A configurable two-tone electron spin resonance spectrometer.

Electron spin resonance (ESR) is a powerful tool for characterizing and manipulating spin systems, but commercial ESR spectrometers can be inflexible and designed to work in narrow frequency bands. This work presents a spectrometer built from off-the-shelf parts that, when coupled with easy-to-design resonators, enables ESR over a broad frequency range, including at frequencies outside the standard bands. It can operate at either a single frequency or at two frequencies simultaneously.

mHealth Gratitude Exercise Mindfulness App for Resiliency Among Neonatal Intensive Care Unit Staff: Three-Arm Pretest-Posttest Interventional Study.

Background: Health care is highly complex and can be both emotionally and physically challenging. This can lead health care workers to develop compassion fatigue and burnout (BO), which can negatively affect their well-being and patient care. Higher levels of resilience can potentially prevent compassion fatigue and BO.

Development of A Standardized Opsonophagocytosis Killing Assay for Group B and Assessment in an Interlaboratory Study.

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

Background: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.

Methods: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring.

Development of the livestock pathogen Trypanosoma (Nannomonas) simiae in the tsetse fly with description of putative sexual stages from the proboscis.

Background: Tsetse-transmitted African animal trypanosomiasis is recognised as an important disease of ruminant livestock in sub-Saharan Africa, but also affects domestic pigs, with Trypanosoma simiae notable as a virulent suid pathogen that can rapidly cause death. Trypanosoma simiae is widespread in tsetse-infested regions, but its biology has been little studied compared to T. brucei and T.

Evidence from UK Research Ethics Committee members on what makes a good research ethics review, and what can be improved.

The rapid development of vaccines and other innovative medical technologies in response to the COVID-19 pandemic required streamlined and efficient ethics and governance processes. In the UK the Health Research Authority (HRA) oversees and coordinates a number of the relevant research governance processes including the independent ethics review of research projects. The HRA was instrumental in facilitating the rapid review and approval of COVID-19 projects, and following the end of the pandemic, have been keen to integrate new ways of working into the UK Health Departments' Research Ethics Service.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. We interviewed ( = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively.

Simplifying complex fault data for systems-level analysis: Earthquake geology inputs for U.S. NSHM 2023.

As part of the U.S. National Seismic Hazard Model (NSHM) update planned for 2023, two databases were prepared to more completely represent Quaternary-active faulting across the western United States: the NSHM23 fault sections database (FSD) and earthquake geology database (EQGeoDB).

Cathepsin L Zymogens: Immuno-Proteomic Evidence for Highly Immunogenic Zymogen-Specific Conformational Epitopes to Support Diagnostics Development.

, the common liver fluke and causative agent of zoonotic fasciolosis, impacts on food security with global economic losses of over $3.2 BN per annum through deterioration of animal health, productivity losses, and livestock death and is also re-emerging as a foodborne human disease. Cathepsin proteases present a major vaccine and diagnostic target of the excretory/secretory (ES) proteome, but utilization in diagnostics of the highly antigenic zymogen stage of these proteins is surprisingly yet to be fully exploited.

Ethical Considerations for the Inclusion of Patient-Reported Outcomes in Clinical Research: The PRO Ethics Guidelines.

Importance: Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

Background: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications.

Single-cell transcriptomics reveals expression profiles of Trypanosoma brucei sexual stages.

Early diverging lineages such as trypanosomes can provide clues to the evolution of sexual reproduction in eukaryotes. In Trypanosoma brucei, the pathogen that causes Human African Trypanosomiasis, sexual reproduction occurs in the salivary glands of the insect host, but analysis of the molecular signatures that define these sexual forms is complicated because they mingle with more numerous, mitotically-dividing developmental stages. We used single-cell RNA-sequencing (scRNAseq) to profile 388 individual trypanosomes from midgut, proventriculus, and salivary glands of infected tsetse flies allowing us to identify tissue-specific cell types.

Kinetic and structure-activity studies of the triazolium ion-catalysed benzoin condensation.

Steady-state kinetic and structure-activity studies of a series of six triazolium-ion pre-catalysts 2a-2f were investigated for the benzoin condensation. These data provide quantitative insight into the role of triazolium N-aryl substitution under synthetically relevant catalytic conditions in a polar solvent environment. Kinetic behaviour was significantly different to that previously reported for a related thiazolium-ion pre-catalyst 1, with the observed levelling of initial rate constants to νmax at high aldehyde concentrations for all triazolium catalysts.

Pilot Evaluation of Two Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics.

, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide are threatening the sustainability of the few flukicides presently available, and particularly triclabendazole (TCBZ) as the drug of choice. Consequently, prognoses for future fasciolosis control and sustained TCBZ application necessitate improvements in diagnostic tools to identify anthelmintic efficacy.

Optimising the value of immunomodulatory drugs during induction and maintenance in transplant ineligible patients with newly diagnosed multiple myeloma: results from Myeloma XI, a multicentre, open-label, randomised, Phase III trial.

Second-generation immunomodulatory agents, such as lenalidomide, have a more favourable side-effect profile than the first-generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant-ineligible myeloma (ND-TNE-MM) has not been defined. The most appropriate delivery and dosing regimens of these therapies for patients at advanced age and frailty status is also unclear. The Myeloma XI study compared cyclophosphamide, thalidomide and dexamethasone (CTDa) to cyclophosphamide, lenalidomide and dexamethasone (CRDa) as induction therapy, followed by a maintenance randomisation between ongoing therapy with lenalidomide or observation for patients with ND-TNE-MM.

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial.

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD).

A Mechanistically and Operationally Simple Route to Metal-N-Heterocyclic Carbene (NHC) Complexes.

We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal-N-heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base-assisted concerted process that does not require free NHC formation.

Trial Forge Guidance 2: how to decide if a further Study Within A Trial (SWAT) is needed.

The evidence base available to trialists to support trial process decisions-e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants-is thin.

Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial.

Background: Multiple myeloma has been shown to have substantial clonal heterogeneity, suggesting that agents with different mechanisms of action might be required to induce deep responses and improve outcomes. Such agents could be given in combination or in sequence on the basis of previous response. We aimed to assess the clinical value of maximising responses by using therapeutic agents with different modes of action, the use of which is directed by the response to the initial combination therapy.

Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite Trypanosoma brucei.

The arsenal of drugs used to treat leishmaniasis, caused by spp., is limited and beset by toxicity and emergent resistance. Furthermore, our understanding of drug mode of action and potential routes to resistance is limited.

Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial.

Background: Patients with multiple myeloma treated with lenalidomide maintenance therapy have improved progression-free survival, primarily following autologous stem-cell transplantation. A beneficial effect of lenalidomide maintenance therapy on overall survival in this setting has been inconsistent between individual studies. Minimal data are available on the effect of maintenance lenalidomide in more aggressive disease states, such as patients with cytogenetic high-risk disease or patients ineligible for transplantation.

Trial Forge Guidance 1: what is a Study Within A Trial (SWAT)?

Randomised trials are a central component of all evidence-informed health care systems and the evidence coming from them helps to support health care users, health professionals and others to make more informed decisions about treatment. The evidence available to trialists to support decisions on design, conduct and reporting of randomised trials is, however, sparse. Trial Forge is an initiative that aims to increase the evidence base for trial decision-making and in doing so, to improve trial efficiency.