Relative Forgiveness of Different Allopurinol Implementation Patterns in People with Gout and their Impact on Clinical Outcomes: a Simulation Study.

Background And Objective: Adherence to urate-lowering therapy among people with gout is poor, so it is important to understand which day-to-day medication-taking ('implementation') patterns are most likely to lead to suboptimal serum urate concentrations and worsen clinical outcomes. This study aimed to (1) determine the relative forgiveness (RF) of allopurinol with hypothetical and real-life implementation patterns in people with gout, (2) explore the use of RF as a means of identifying suboptimal implementation patterns, (3) assess the impact of suboptimal implementation patterns on clinical outcomes.

Methods: A simulation study was conducted using a pharmacokinetic-pharmacodynamic model for allopurinol and serum urate to determine the RF of allopurinol implementation patterns.

Evaluating the benefits and risks of puberty blockers and gender-affirming hormones for transgender adolescents.

The use of puberty blockers and gender-affirming hormones by transgender adolescents is the subject of an ongoing public debate. In this paper, we address one central ethical aspect of the debate - the question of what sort of benefits these treatments provide and how to evaluate the significance of these benefits in relation to risks. We argue that the intended benefit of these treatments is best understood as appearance congruence, namely, to create or maintain alignment of physical appearance with one's gender identity.

Weighting of sensory cues reflect changing patterns of visual investment during ecological divergence in butterflies.

Integrating information across sensory modalities enables animals to orchestrate a wide range of complex behaviours. The relative importance placed on one sensory modality over another reflects the reliability of cues in a particular environment and corresponding differences in neural investment. As populations diverge across environmental gradients, the reliability of sensory cues may shift, favouring divergence in neural investment and the weight given to different sensory modalities.

Easing the way to achieving target serum urate in people with gout: protocol for a non-inferiority randomised strategy trial using an allopurinol dosing model in Aotearoa/New Zealand (the Easy-Allo Study).

Introduction: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.

Justifying Responses Affects the Relationship Between Confidence and Accuracy.

How confident a student is about how they answer a question has important education implications. Participants answered 10 mathematics questions and provided their estimates of how likely they got each individual item correct and how many, in total, they answered correctly. They were overconfident in these metacognitive judgments.

Potent immunogenicity and protective efficacy of a multi-pathogen vaccination targeting Ebola, Sudan, Marburg and Lassa viruse.

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths.

Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction.

Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g.

Leverage points for establishing clinical decision-maker as a vital component of pharmacists' professional identity.

This commentary explores how a change in the professional identity of pharmacists from medicines supplier to clinical decision-maker might take place. Three leverage points are identified that support this change. The first leverage point involves workplace culture.

Low-dose infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates.

Introduction: Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund's Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied.

The experiences and perspectives of people with gout on urate self-monitoring.

Introduction: Gout management remains suboptimal despite safe and effective urate-lowering therapy. Self-monitoring of urate may improve gout management, however, the acceptability of urate self-monitoring by people with gout is unknown. The aim of this study was to explore the experiences of urate self-monitoring in people with gout.

Selection drives divergence of eye morphology in sympatric Heliconius butterflies.

When populations experience different sensory conditions, natural selection may favor sensory system divergence, affecting peripheral structures and/or downstream neural pathways. We characterized the outer eye morphology of sympatric Heliconius butterflies from different forest types and their first-generation reciprocal hybrids to test for adaptive visual system divergence and hybrid disruption. In Panama, Heliconius cydno occurs in closed forests, whereas Heliconius melpomene resides at the forest edge.

Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine in adults in Kenya: a phase 1/2 single-blind, randomised controlled trial.

Background: There are limited data on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in African populations. Here we report the immunogenicity and safety of the ChAdOx1 nCoV-19 (AZD1222) vaccine from a phase 1/2 single-blind, randomised, controlled trial among adults in Kenya conducted as part of the early studies assessing vaccine performance in different geographical settings to inform Emergency Use Authorisation.

Methods: We recruited and randomly assigned (1:1) 400 healthy adults aged ≥18 years in Kenya to receive ChAdOx1 nCoV-19 or control rabies vaccine, each as a two-dose schedule with a 3-month interval.

Anesthesia-Related Closed Claims in Free-Standing Ambulatory Surgery Centers.

Background: As higher acuity procedures continue to move from hospital-based operating rooms (HORs) to free-standing ambulatory surgery centers (ASCs), concerns for patient safety remain high. We conducted a contemporary, descriptive analysis of anesthesia-related liability closed claims to understand risks to patient safety in the free-standing ASC setting, compared to HORs.

Methods: Free-standing ASC and HOR closed claims between 2015 and 2022 from The Doctors Company that involved an anesthesia provider responsible for the claim were included.

Psychometric evaluation of the Trust in Science and Scientists Scale.

Reliable and valid measurement of trust in science and scientists is important. Assessing levels of such trust is important in determining attitudes and predicting behaviours in response to medical and scientific interventions targeted at managing public crises. However, trust is a complex phenomenon that has to be understood in relation to both distrust and mistrust.

The impact of peritoneal dialysis on oxypurinol and urate elimination in people with gout.

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial.

Background: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development.

Patient-Led Urate Self-Monitoring to Improve Clinical Outcomes in People With Gout: A Feasibility Study.

Objective: Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life.

Methods: People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.

From wires to waves, a novel sensor system for in vivo pressure monitoring.

Pressure monitoring in various organs of the body is essential for appropriate diagnostic and therapeutic purposes. In almost all situations, monitoring is performed in a hospital setting. Technological advances not only promise to improve clinical pressure monitoring systems, but also engage toward the development of fully implantable systems in ambulatory patients.

Adaptive introgression of a visual preference gene.

Visual preferences are important drivers of mate choice and sexual selection, but little is known of how they evolve at the genetic level. In this study, we took advantage of the diversity of bright warning patterns displayed by butterflies, which are also used during mate choice. Combining behavioral, population genomic, and expression analyses, we show that two species have evolved the same preferences for red patterns by exchanging genetic material through hybridization.

Estimation of adherence to urate-lowering therapy in people living with gout using Australia's Pharmaceutical Benefits Scheme and patient-reported dosing.

Aims: The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day).

Methods: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%.

The development and evaluation of dose-prediction tools for allopurinol therapy (Easy-Allo tools).

Aims: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient dose-escalation strategies. The aim of this research was to develop and externally evaluate allopurinol dosing tools, one for use when the pre-urate-lowering therapy serum urate is known (Easy-Allo1) and one for when it is not known (Easy-Allo2).

Quantifying visual acuity in butterflies.

butterflies are well-known for their colourful wing patterns, which advertise distastefulness to potential predators and are used during mate choice. However, the relative importance of different aspects of these signals will depend on the visual abilities of and their predators. Previous studies have investigated colour sensitivity and neural anatomy, but visual acuity (the ability to perceive detail) has not been studied in these butterflies.

The Sensory Ecology of Speciation.

In this work, we explore the potential influence of sensory ecology on speciation, including but not limited to the concept of sensory drive, which concerns the coevolution of signals and sensory systems with the local environment. The sensory environment can influence individual fitness in a variety of ways, thereby affecting the evolution of both pre- and postmating reproductive isolation. Previous work focused on sensory drive has undoubtedly advanced the field, but we argue that it may have also narrowed our understanding of the broader influence of the sensory ecology on speciation.