Efficacy, Safety and Tolerability of Volixibat, an IBAT Inhibitor, in Patients With Intrahepatic Cholestasis of Pregnancy

ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) presents with cholestatic pruritus, elevated sBA and increased risk of adverse perinatal outcomes. Volixibat is a minimally absorbed IBAT inhibitor that interrupts enterohepatic recirculation. We describe four patients with ICP with pruritus and sBA > ULN treated with volixibat (20 or 80 mg BID orally until delivery), with dose modifications permitted for tolerability. Daily pruritus scores, sBA, liver enzymes, perinatal outcomes and TEAEs were assessed. Over 1000 patients were invited to participate; 26 were screened, and four received volixibat. Three patients experienced reductions in pruritus from baseline regardless of volixibat dose, with intermittent relief coinciding with resumption of dosing when doses were interrupted. sBA nadir values all reached < 6 μmol/L following volixibat. No clinically meaningful changes in laboratory parameters were observed. All patients had healthy live births. Most frequent TEAEs were gastrointestinal. Volixibat demonstrated improvements in pruritus and sBA in patients with ICP. Trial Registration: NCT04718961

Relations Between Preferential Looking to Synchronous Audiovisual Speech and Expressive Language in Infants With Autistic and Non‐Autistic Siblings

ABSTRACT Differences in audiovisual processing may influence language development in autism. We characterized preferential looking to temporally synchronous audiovisual speech in fifty infants (28 elevated‐likelihood [54% male]; 22 population‐level‐likelihood [50% male]) aged 12–18 months. We first tested whether preferential looking to synchronous audiovisual speech differed between groups; population‐level‐likelihood infants demonstrated greater preferential looking to synchronous audiovisual speech relative to elevated‐likelihood infants by 18 months. We then assessed whether preferential looking to synchronous audiovisual speech was related to concurrent expressive language (1) directly, (2) via vocalization complexity, and (3) as moderated by age, sex, and familial likelihood group. Infants completed an eye tracking task and standardized communication and language assessments at 12–18 months. The population‐level‐likelihood infants demonstrated greater preferential looking to synchronous audiovisual speech relative to elevated‐likelihood infants by 18 months. Preferential looking to synchronous audiovisual speech was not directly and unconditionally associated with concurrent expressive language. However, moderation and mediation analyses showed that preferential looking to synchronous audiovisual speech was significantly associated with concurrent expressive language through increased vocalization complexity in male infants. Implications for research, theory, and clinical practice are discussed.

Caregiver Screening for Relapse Among Children Recently Recovered From Severe Acute Malnutrition: A Randomized Controlled Feasibility Trial

ABSTRACT Relapse to acute malnutrition after recovery from severe acute malnutrition (SAM) is common. However, most programmatic resources are devoted to the acute phase of recovery, and fewer interventions are available for children recently discharged from outpatient nutritional programs. We evaluated the feasibility of training caregivers to screen for relapse using mid‐upper arm circumference (MUAC) tapes for reducing time to detection of relapse among children recently recovered from SAM in Burkina Faso. Caregiver‐child dyads were enrolled and randomized in a 1:1 fashion to either caregiver MUAC screening or local standard of care (SOC), which consists of monthly clinic‐based follow‐up visits for 3 months following discharge. In the MUAC screening group, caregivers were trained on how to use a standard MUAC tape and asked to screen their child weekly with a provided MUAC tape for the 6‐month duration of the study. The primary outcome was time to relapse detection, defined as MUAC < 12.5 cm and/or weight‐for‐height Z‐score < −2. Secondary outcomes included hospitalization and/or death over the 6‐month study period. Of 200 caregiver‐child dyads enrolled in the trial, 99 were randomized to the MUAC screening group and 101 to the SOC group. By 6 months after enrollment, the hazard of relapse detection was lower in the MUAC screening group compared to the SOC group (hazard ratio, HR, 0.65, 95% confidence interval, CI, 0.38–1.12). Fewer hospitalizations and/or deaths occurred in the MUAC screening group compared to the SOC group (MUAC: 3%; SOC: 14%, risk ratio 0.23, 95% CI, 0.07–0.79). Training caregivers to screen for relapse after recovery from SAM was feasible and may lead to modestly reduced time to detection of relapse, suggesting a full‐scale trial is warranted. Trial Registration: This study was prospectively registered on clinicaltrials.gov (NCT05932992, registered June 27, 2023).

Genetic Surveillance Reveals Differential Evolutionary Dynamic of Anopheles gambiae Under Contrasting Insecticidal Tools Used in Malaria Control

ABSTRACT Malaria, a febrile disease caused by the Plasmodium parasites and transmitted by mosquitoes, is a leading cause of mortality in children under 5 in endemic countries. The widespread deployment of insecticide‐treated bed nets (ITNs) has significantly reduced malaria transmission, but rising levels of insecticide resistance threaten to halt the progress. Monitoring insecticide resistance is vital for effective vector control, particularly when deploying new tools. Understanding mosquito population responses to these interventions is crucial for guiding control programmes in making informed decisions about the selection, timing and geographic deployment of tools. This genomic study investigates the demographic and evolutionary consequences on the malaria vector Anopheles gambiae of deploying standard ITNs (containing only pyrethroids) and pyrethroid‐PBO nets (containing pyrethroids plus the synergist piperonyl butoxide) during a clinical trial in Uganda. Despite substantial reductions in indoor mosquito densities in the clinical trial, estimates of nucleotide diversity (π) and linkage disequilibrium revealed no significant decline in effective population size, reflecting continued large population size even after effective control. Marked allele frequency shifts at resistance‐associated loci indicated strong selection pressures driven by the interventions, with distinct selective dynamics between the two net types, highlighting alternative pyrethroid detoxification pathways in the presence of PBO. A duplication in the Cyp9k1 gene significantly increased in frequency in populations exposed to pyrethroid‐only nets but decreased in populations exposed to PBO‐treated nets, suggesting that selection for over‐expression of this gene is removed when this resistance mechanism is impacted by PBO. An alternative potential detoxification mechanism was selected within a region of the 2La chromosomal inversion on chromosome 2 L, which encompasses the UDP‐glucose 6‐dehydrogenase gene. This variant consistently increased in frequency when exposed to PBO‐treated nets. Additionally, pyrethroid‐only nets selected for a novel locus on the X chromosome containing the diacylglycerol kinase gene, which is potentially linked to behavioural adaptations through its role in neurotransmission modulation. Our findings underscore the importance of genomic surveillance in vector control, revealing distinct evolutionary dynamics of insecticide resistance mechanisms in the presence of PBO. While ITNs remain effective, the persistence and evolution of resistance‐associated alleles highlight the need for adaptive and dynamic resistance management strategies. By integrating high‐resolution genomic data with epidemiological and entomological monitoring, this study offers actionable insights to sustain malaria control efforts amid the ongoing challenge of insecticide resistance.

Combining Population Genomics With Ancient DNA to Understand Island Colonisation History of the Madagascar Turtle Dove

ABSTRACT The Mascarene archipelago (Mauritius, Reunion and Rodrigues), characterised by first human arrival being recent, offers a unique setting to study species colonisation on a recent timescale, and contribution of past human interventions. Here we use a combination of modern and ancient DNA data as a case study to investigate the colonisation history of a species of concern in relation to conservation programmes—the Madagascar turtle dove ( Nesoenas picturata ) on Mauritius and Reunion. We generated a reference genome and re‐sequenced genomes from contemporary N. picturata populations, as well as genome‐wide data from relevant subfossils. A combination of model‐free inferences, site frequency spectrum (SFS) based demographic modelling, and analyses of population structure including that of subfossils indicate that N. picturata colonised both islands independently and naturally from Madagascar, long before human arrival. Summary statistics and SFS‐based modelling reveal large effective population sizes ( Ne ) and high genetic diversity in island populations, conflicting with historical accounts of human‐induced demographic collapse. Based on goodness‐of‐fit, genetic structure and diversity indices do not discriminate between two best‐fitting models, one of which posits large recent Ne and negligible translocation rates, while the other supports recent severe bottlenecks followed by high post‐human translocation from Madagascar. Nonetheless, linkage disequilibrium provides stronger evidence for the latter scenario, which may also explain high genetic diversity. Both modern and ancient DNA data sources independently support the classification of N. picturata as native to both islands. Our findings highlight the potential of resolving colonisation history on timescales that have often been too recent for resolution, using a combination of different data sources, and by validating demographic models with multiple summary statistics.

The development of medical students' professional identities in rural settings: A scoping review

Abstract Background Major documented disparities exist in health equity between individuals living in rural and metropolitan areas. Recruiting and retaining doctors in rural areas remains a considerable challenge. Students' exposure to rural experiences facilitates their development of professional identities aligned to this specific community of practice. Although previous studies have explored medical students' identity development in rural settings, a comprehensive picture of the development of medical students' professional identities in rural settings is yet to be established. Our study aims to address this, and as such, a scoping review was conducted to map the existing literature in this area. Methods Our review follows the Joanna Briggs Institute methodology, with reporting being guided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for Scoping Reviews. We searched MEDLINE, Embase, Web of Science and PsycINFO databases. We use inductive thematic analysis to synthesise the evidence with reference to the review questions. We present our results based on our developed framework. Results We identified 1085 publications with 20 fully meeting the inclusion criteria. The majority of included studies were published in the last 9 years, originating from Australia, South Africa and the United States. These are based on voluntary rural medical placements, with the commonest placement duration being 12 months. Included publications predominantly use qualitative methodologies, most commonly individual and/or group interviews. Only two of the included studies use an approach informed by established theories of identity development. We used inductive thematic analysis of the included studies, identifying three related themes: Acting Up , Rural Community and Feeling of Fit . Fewer than half of the included studies referenced students' future intention to practice rurally, and no paper specifically examined an association between students' professional identity and intention to practice rurally. Discussion It is a core remit of medical education to include professional identity as a key outcome. In a rural context, understanding the role that professional identity plays in medical students' future career choices may be key to understanding workforce maldistribution. Existing medical student identities research tends to lack theoretical grounding and alignment; subsequently failing to comprise a homogenous body of literature essential for facilitating our comprehensive understanding of professional identity, which is necessary for advancements within this field.

Recent Acoustic Detection of Eubalaena japonica South of the Bering Strait

Characterising Hand Tremor in Adult Kidney Transplant Recipients: Its Impact on Daily Activities and Relationship With Tacrolimus Administration and Exposure

ABSTRACT Aim This study aimed to characterise hand tremor and examine its relationship with tacrolimus administration time and systemic exposure in adult kidney transplant recipients early post‐transplantation. Methods Quantitative and qualitative data on hand tremor were collected from patients receiving immediate‐release tacrolimus, approximately 1 month post‐transplantation. Smartphone accelerometry was used to objectively assess tremor pre‐ and 2 h post‐tacrolimus administration and values were compared using a Wilcoxon signed‐rank test. A Welch's analysis of variance (ANOVA) was used to determine if tacrolimus trough concentration ( C 0 ), 2 h post‐dose concentration ( C 2 ) and the ratio of C 2 / C 0 were significantly different between patients reporting no, mild or moderate/severe tremor. Results One hundred and seven patients enrolled in the study. Eighty percent of patients reported hand tremor, often during voluntary hand movement. Thirty‐eight percent said it interfered with daily activities, impeding their ability to perform basic daily tasks required for eating, drinking, accessing medicines and working. Hand tremor was not more severe at 2 h post‐tacrolimus intake. Tacrolimus exposure was not associated with patient‐reported tremor severity. Significantly greater amplitude and power in hand movement were detectable by smartphone accelerometry in patients reporting hand tremor. Conclusion Hand tremor is highly prevalent early post‐transplantation and has a major impact on patient functionality and quality of life. Further research is needed to develop novel tacrolimus exposure estimates that better correlate with tremor, and to identify improved ways to clinically assess, manage and mitigate the impact of hand tremor following transplantation. Smartphone accelerometry may be a useful tool in assessing tremor in future studies.

Vaccination in the Age of Memes: An Exploration of Digital Health Communication

ABSTRACT This study explores how internet memes serve as digital communication tools in public health discourse, influencing public perceptions by spreading both accurate and misleading health information. Utilizing a dual qualitative approach, Qualitative Content Analysis (QCA) and Reflexive Thematic Analysis (RTA), this study examined 99 vaccine‐related memes shared online during the 2019 and 2025 measles outbreaks and the 2020 COVID‐19 pandemic. QCA analyzed rhetorical tones (pathos, ethos, and logos) and vaccine stances (pro, anti, and neutral), while RTA identified key themes. Memes were sampled from Google Images using broad vaccine‐related search terms (e.g., “vaccine meme,” “vaccination meme”), allowing inclusion of memes related to a wide range of vaccine‐preventable diseases rather than limiting the dataset to any single condition. While memes predominantly targeted emotional appeals (pathos), emergent themes include increased use of logical appeals (logos), political polarization, and anti‐vaccine sentiments. Nurses and other public health communicators must counter misinformation and foster evidence‐based dialogue to shape digital health literacy. Rhetorical patterns (e.g., humor, emotional resonance, and appeals to credibility) are communication strategies that transcend national boundaries. These findings, therefore, provide a foundation for understanding how similar dynamics might appear in other linguistic and cultural settings, while highlighting the need for ongoing research.

The frequency and importance of polyploidy in tropical rainforest tree radiations

Summary The presence of more than two copies of the genome in an organism, termed ‘polyploidy’, is a crucial force in plant evolution, generating genetic, phenotypic and ecological diversity. [Correction added on 22 January 2026, after first online publication: the preceding sentence has been corrected.] The Amazonian tree flora is the most species‐rich on Earth and largely arose as a result of rapid evolutionary radiations. While polyploidy is an important catalyst of rapid radiations, it remains poorly studied in tropical tree radiations. We examined ploidy variation across Inga (Fabaceae), a characteristic Amazonian tree radiation, using DNA‐sequence data from 1305 loci for 189/282 Inga species. We then tested whether polyploid species experience more positive selection than diploids, particularly in loci underlying chemical defence against herbivory, which is a key ecological pressure affecting rainforest tree diversification. We show that tetraploidy occurs in 15% ( n  = 29) of the Inga species we studied, with several widespread species showing geographical ploidy variation, alongside minimal phylogenetic signal in ploidy which suggests recurrent polyploidisation. Interestingly, we found more loci under selection in polyploids than in diploids, most notably in chemical defence loci. Our results show that polyploidy has arisen independently in several Inga species, and that polyploidisation can lead to elevated selection in chemical defence, helping to shape ecological interactions and influence diversification in Inga .