Explore the vast range of titles available.

Aluminosilicates (kyanite, sillimanite and andalusite) are useful pressure–temperature (P–T) indicators that can form in a range of rock types through different mineral reactions, including those that involve partial melting. However, the presence of xenocrystic or inherited grains may lead to spurious P–T interpretations. The morphologies, microtextural positions, cathodoluminescence responses and trace element compositions of migmatite-hosted kyanite from Eastern Bhutan were investigated to determine whether sub-solidus kyanite could be distinguished from kyanite that crystallised directly from partial melt, or from kyanite that grew peritectically during muscovite dehydration reactions. Morphology and cathodoluminescence response were found to be the most reliable petrogenetic indicators. Trace element abundances generally support petrographic evidence, but protolith bulk composition exerts a strong control over absolute element abundance in kyanite. Sample-normalised concentrations show distinctive differences between petrogenetic types, particularly for Mg, Ti, V, Cr, Mn, Fe and Ge. LA-ICP-MS element maps, particularly combined to show Cr/V, provide additional information about changing geochemical environments during kyanite growth. Most kyanite in the studied migmatitic leucosomes is of sub-solidus origin, with less widespread evidence for peritectic crystallisation. Where present, grain rims commonly crystallised directly from the melt; however, entire grains crystallised exclusively from melt are rare. The presence of kyanite in leucosomes does not, therefore, necessarily constrain the P–T conditions of melting, and the mechanism of growth should be determined before using kyanite as a P–T indicator. This finding has significant implications for the interpretation of kyanite-bearing migmatites as representing early stages of melting during Himalayan evolution.

Eclogites from the deepest structural levels beneath the Semail ophiolite, Oman, record the subduction and later exhumation of the Arabian continental margin. Published ages for this high pressure event reveal large discrepancies between the crystallisation ages of certain eclogite-facies minerals and apparent cooling ages of micas. We present precise U-Pb zircon (78.95 +/- 0.13 Ma) and rutile (79.6 +/- 1.1 Ma) ages for the eclogites, as well as new U-Pb zircon ages for trondhjemites from the Semail ophiolite (95.3 +/- 0.2 Ma) and amphibolites from the metamorphic sole (94.48 +/- 0.23 Ma). The new eclogite ages reinforce published U-Pb zircon and Rb-Sr mineral-whole rock isochron ages, yet are inconsistent with published interpretations of older 40Ar/39Ar phengite and Sm-Nd garnet dates. We show that the available U-Pb and Rb-Sr ages, which are in tight agreement, fit better with the available geological evidence, and suggest that peak metamorphism of the continental margin occurred during the later stages of ophiolite emplacement.[PUBLICATION ABSTRACT]

Researchers in the UK are taking on new roles and responsibilities to meet the requirements of an expanded agenda for generating and evidencing social and economic impacts from research. Within this wider context, culture change programmes have identified learning as an important driver of change. Here we outline a professional development programme designed to train postgraduate researchers studying environmental sciences in core engagement, influence and impact, governance and organization skills for research. We argue that training is an important step in further catalysing progressive culture change. However, our research- and experience-informed critical reflections in supporting researchers suggest that there is still significant work to be done: (1) to offer consistent messages to researchers at all grades about social impacts from research and (2) to ensure that engagement is seen as an aspirational activity, embedded within research.

Aboriginal and Torres Strait Islander (collectively, Indigenous Australian) women experience a higher burden of cervical cancer than other women. The National Cervical Screening Program (NCSP) is failing to meet the needs of Indigenous Australian women, resulting in many women not regularly participating in cervical screening. However, one third of Indigenous Australian women do participate in cervical screening. The reasons that some women in this population commence and continue to screen remain unheard but could provide insights to support women who currently do not participate. We aimed to describe Indigenous Australian women's experiences and views of participation in cervical screening by yarning (a culturally-appropriate interview technique) with 50 Indigenous Australian women aged 25-70 years who had completed cervical screening in the past five years, recruited via Primary Health Care Centres (PHCCs) from three jurisdictions. Aboriginal or Torres Strait Islander women researchers conducted the interviews. Thematic analysis identified six themes: screening as a means of staying strong and in control; overcoming fears, shame, and negative experiences of screening; needing to talk openly about screening; the value of trusting relationships with screening providers; logistical barriers; and overcoming privacy concerns for women employed at PHCCs. Despite describing screening as shameful, invasive, and uncomfortable, women perceived it as a way of staying healthy and exerting control over their health. This ultimately supported their participation and a sense of empowerment. Women valued open discussion about screening and strong relationships with health providers. We identified logistical barriers and specific barriers faced by women employed at PHCCs. This study is strengthened by a research approach that centred Indigenous Australian women's voices. Understanding the experiences of Indigenous Australian women who participate in screening will help screening providers support women to start and continue to screen regularly. Recommendations for practice are provided.

Aboriginal and Torres Strait Islander women have lower participation in Australia’s National Cervical Screening Program than other Australian women. Under-screened (including never screened) women’s voices are rarely heard in research evidence, despite being a priority group for interventions to increase cervical screening participation. This study aimed to describe under-screened Aboriginal and Torres Strait Islander women’s perspectives on cervical screening. Participants were 29 under-screened (women who had either never screened, had not screened in the previous five years or had recently screened in the past three months after more than five years) Aboriginal and Torres Strait Islander women from five communities across three states/territories. Female Aboriginal and Torres Strait Islander researchers Yarned with women about why they did not participate in screening and how to improve screening. Yarning is an Indigenous qualitative research method in which relationships and trust facilitate culturally safe conversation. Transcripts were analysed thematically. The proportion of eligible women who screened within 30 days after the Yarn was calculated. We identified four themes describing how the harms outweighed the benefits of cervical screening for under-screened women. These were: 1) distress, discomfort, and trauma; 2) lack of privacy and control; 3) complicated relationships with health care providers (HCPs); and 4) pressured, insensitive, and/or culturally unsafe communication from HCPs. Under-screened women who had recently screened had maintained privacy and control through self-collection and had experienced trauma-informed and empathetic care from their HCPs. While we cannot unequivocally attribute women’s subsequent participation in screening to their involvement in this study, it is notable that one third of eligible under-screened women were screened within 30 days after the Yarn. Enhancing privacy, implementing trauma-informed approaches to care and sensitivity to the clinician-client relationship dynamics could enhance women’s sense of comfort in, and control over, the screening procedure. The opportunity to Yarn about cervical screening and self-collection may address these issues and support progress toward cervical cancer elimination in Australia.

MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155-deficient CD4⁺ T cells identified a wide spectrum of microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system.

Escalating mental health demand exceeds existing clinical capacity, necessitating scalable digital solutions. However, engagement remains challenging. Conversational agents can enhance engagement by making digital programs more interactive and personalized, but they have not been widely adopted. This study evaluated a digital program for anxiety in comparison to external comparators. The program used an artificial intelligence (AI)-driven conversational agent to deliver clinician-written content via machine learning, with clinician oversight and user support. This study aims to evaluate the engagement, effectiveness, and safety of this structured, evidence-based digital program with human support for mild, moderate, and severe generalized anxiety. Statistical analyses sought to determine whether the program reduced anxiety more than a propensity-matched waiting control and was statistically noninferior to real-world, propensity-matched face-to-face and typed cognitive behavioral therapy (CBT). Prospective participants (N=299) were recruited from the National Health Service (NHS) or social media in the United Kingdom and given access to the digital program for up to 9 weeks (study conducted from October 2023 to May 2024). End points were collected before, during, and after the digital program, as well as at a 1-month follow-up. External comparator groups were created through propensity matching of the digital program sample with NHS Talking Therapies (NHS TT) data from ieso Digital Health (typed CBT) and Dorset HealthCare (DHC) University NHS Foundation Trust (face-to-face CBT). Superiority and noninferiority analyses were conducted to compare anxiety symptom reduction (change on the 7-item Generalized Anxiety Disorder Scale [GAD-7]) between the digital program group and the external comparator groups. The program included human support, and clinician time spent per participant was calculated. Participants used the program for a median of 6 hours over 53 days, with 232 of the 299 (77.6%) engaged (ie, completing a median of 2 hours over 14 days). There was a large, clinically meaningful reduction in anxiety symptoms for the digital program group (per-protocol [PP; n=169]: mean GAD-7 change -7.4, d=1.6; intention-to-treat [ITT; n= 99]: mean GAD-7 change -5.4, d=1.1). The PP effect was statistically superior to the waiting control (d=1.3) and noninferior to the face-to-face CBT group (P<.001) and the typed CBT group (P<.001). Similarly, for the ITT sample, the digital program showed superiority to waiting control (d=0.8) and noninferiority to face-to-face CBT (P=.002), with noninferiority to typed CBT approaching significance (P=.06). Effects were sustained at the 1-month follow-up. Clinicians overseeing the digital program spent a mean of 1.6 hours (range 31-200 minutes) of clinician time in sessions per participant. By combining AI and human support, the digital program achieved clinical outcomes comparable to human-delivered care, while significantly reducing the required clinician time by up to 8 times compared with global care estimates. These findings highlight the potential of technology to scale evidence-based mental health care, address unmet needs, and ultimately impact quality of life and reduce the economic burden globally. ISRCTN Registry ISRCTN52546704; http://www.isrctn.com/ISRCTN52546704.

Subsurface datasets typically lack the resolution or coverage to adequately sample fracture networks in 3D, and fracture properties are typically extrapolated from available data (e.g. seismic data or wellbore image logs). Here we assess the applicability of extrapolating fracture properties (orientation, length, and intensity) across observation scales in deformed, mechanically layered carbonate rocks. Data derived from high-resolution field images, medium-resolution digital outcrop data, and relatively low-resolution satellite imagery at Swift Reservoir anticline, NW Montana are leveraged to (i) assess interacting structural and stratigraphic controls on fracture development, and (ii) compare estimated fracture properties derived from multiple observation scales. We show that hinge-parallel and hinge-perpendicular fractures (i) make up the majority of fractures at the site; (ii) are consistently oriented with respect to the fold hinge, despite along-strike variability in the fold hinge orientation; and (iii) exhibit systematic increases in intensity towards the anticline hinge. These fractures are interpreted as having formed during folding. Other fractures recorded at the site exhibit inconsistent orientations, show no systematic trends in fracture intensity, and are interpreted as being unrelated to fold formation. Fracture orientation data exhibit the greatest agreement across observation scales at hinge and forelimb positions, where hinge-parallel and hinge-perpendicular fracture sets are well developed, and little agreement on the anticline backlimb, where fracture orientations are less predictable and more dispersed. This indicates that the scaling of fracture properties at Swift Reservoir anticline is spatially variable and partly dependent on structural position. Our results suggest that accurate prediction and extrapolation of natural fracture properties in contractional settings requires the assessment of structural position, lithologic variability, and spatially variable fracture scaling relationships, as well as consideration of the deformation history before and after folding.

Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood. Primary prostate tumours are known to be genetically heterogeneous and clonal selection has the potential to drive metastasis. Here Hong et al . show that the acquisition of TP53 mutations is linked to clonal expansion and metastatic progression to lethality.