Understanding the mechanisms behind the remote triggering of landslides by seismic waves at micro-strain amplitude is essential for quantifying seismic hazards. Granular materials provide a relevant model system to investigate landslides within the unjamming transition framework, from solid to liquid states. Furthermore, recent laboratory experiments have revealed that ultrasound-induced granular avalanches can be related to a reduction in the interparticle friction through shear acoustic lubrication of the contacts. However, investigating slip at the scale of grain contacts within an optically opaque granular medium remains a challenging issue. Here, we propose an original coupling model and numerically investigate two-dimensional dense granular flows triggered by basal acoustic waves. We model the triggering dynamics at two separated time scales – one for grain motion (milliseconds) and the other for ultrasound (10 ${\rm \mu} {\rm s}$) – relying on the computation of vibrational modes with a discrete element method through the reduction of the local friction. We show that ultrasound predominantly propagates through the strong-force chains, while the ultrasound-induced decrease of interparticle friction occurs in the weak contact forces perpendicular to the strong-force chains. This interparticle friction reduction initiates local rearrangements at the grain scale that eventually lead to a continuous flow through a percolation process at the macroscopic scale – with a delay depending on the proximity to the failure. Consistent with experiments, we show that ultrasound-induced flow appears more uniform in space than pure gravity-driven flow, indicating the role of an effective temperature by ultrasonic vibration.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Tightly focused proton beams generated from helical coil targets have been shown to be highly collimated across small distances, and display characteristic spectral bunching. We show, for the first time, proton spectra from such targets at high resolution via a Thomson parabola spectrometer. The proton spectral peaks reach energies above 50 MeV, with cutoffs approaching 70 MeV and particle numbers greater than 10${}^{10}$. The spectral bunch width has also been measured as low as approximately 8.5 MeV (17% energy spread). The proton beam pointing and divergence measured at metre-scale distances are found to be stable with the average pointing stability below 10 mrad, and average half-angle beam divergences of approximately 6 mrad. Evidence of the influence of the final turn of the coil on beam pointing over long distances is also presented, corroborated by particle tracing simulations, indicating the scope for further improvement and control of the beam pointing with modifying target parameters.

A Bayesian procedure is given for estimation in unrestricted common factor analysis. A choice of the form of the prior distribution is justified. It is shown empirically that the procedure achieves its objective of avoiding inadmissible estimates of unique variances, and is reasonably insensitive to certain variations in the shape of the prior distribution.

Past hydrogeological processes and human impacts may exert substantial memory effects on today’s groundwater systems. Thorough characterization of such long-term processes is required for scientists and policymakers to predict the hydrogeological impacts of land management options. Especially in data-scarce areas, historical data are essential to unravel long-term hydrogeological processes, which could not be identified by short-term fieldwork or model simulations alone. However, historical data are often overlooked or only used as background information in most hydrogeological studies. We show that the combination of historical reports and quantitative data yields major insights in the hydrogeological system of Curaçao, a small semi-arid Caribbean island. Reconstructing the island’s groundwater conditions over the past 500 years revealed that deforestation and excessive abstraction has had a detrimental effect on the island’s groundwater reserves. Historical notes and data revealed major signs of seawater intrusion, especially during abstraction peaks in the island’s industrial era. Intrusion effects are still observed locally on the island today, but additional groundwater recharge by waste water has caused freshening elsewhere. We hypothesize that the observed aquifer replenishment locally enhances submarine groundwater discharge, flushing accumulated nutrients and pollutants towards Curaçao’s fringing coral reefs. We expect that this study’s insights motivate more hydrogeologists to use historical reports and data in future studies.

In the winter of 2022–2023, hundreds of the Atlantic puffins (Fratercula arctica) appeared dead in the coast of the Canary Islands, a rare event considering their cold-living habits, normally occupying the North Atlantic Ocean. In this work, investigation about the parasites present in the Atlantic puffins found in the biggest islands of the Archipelago was carried out from a population portion. Necropsies of 39 birds were made and, during the examination of the urinary tracts, helminths were found. Morphoanatomical analysis under microscope allowed to identify them into Renicola genus with high similarity to Renicola sloanei. After that, DNA was extracted and NADH dehydrogenase subunit 1 gene were amplificated by a polymerase chain reaction method followed by sequencing and phylogenetic analysis. The molecular results demonstrated that in fact R. sloanei was the helminth parasite present in the urinary tracts of the Atlantic puffins found in the Canary Islands.

Visceral leishmaniasis (VL) is a tropical disease that can be fatal if acute and untreated. Diagnosis is difficult, the treatment is toxic and prophylactic vaccines do not exist. Leishmania parasites express hundreds of proteins and several of them are relevant for the host's immune system. In this context, in the present study, 10 specific T-cell epitopes from 5 parasite proteins, which were identified by antibodies in VL patients’ sera, were selected and used to construct a gene codifying the new chimeric protein called rCHI. The rCHI vaccine was developed and thoroughly evaluated for its potential effectiveness against Leishmania infantum infection. We used monophosphoryl lipid A (MPLA) and polymeric micelles (Mic) as adjuvant and/or delivery system. The results demonstrated that both rCHI/MPLA and rCHI/Mic significantly stimulate an antileishmanial Th1-type cellular response, with higher production of IFN-γ, TNF-α, IL-12 and nitrite in vaccinated animals, and this response was sustained after challenge. In addition, these mice significantly reduced the parasitism in internal organs and increased the production of IgG2a isotype antibodies. In vivo and in vitro toxicity showed that rCHI is safe for the mammalians, and the recombinant protein also induced in vitro lymphoproliferative response and production of Th1-type cytokines by human cells, which were collected from healthy subjects and treated VL patients. These data suggest rCHI plus MPLA or micelles could be considered as a vaccine candidate against VL.

Objectives: To evaluate the effect and safety of Cannabidiol (CBD) on behavioral and psychological symptoms in elderly with Vascular dementia (VD).

Methods: Double- blind, randomized, placebo-controlled clinical trial involving elderly patients with VD at the psychogeriatrics and vascular dementia outpatient clinic at Hospital das Clínicas de Ribeirão Preto. The intervention evaluated was the use of CBD 300mg/day compared to placebo. The instruments used are: Neuropsychiatric Inventory, Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale, Side Effects Scale, Mini- Mental State Examination, Brief Cognitive Screening Battery, Katz Index of Independence in Activities of Daily Living, Lawton Instrumental Activities of Daily Living Scale, Informant Questionnaire on Cognitive Decline in the Elderly, Zarit Burden Inventory. The included participants were assessed at the beginning of the study (baseline assessment), in the first, second and fourth weeks after the start of the clinicaltrial.

Results: 30 participants were included. The mixed ANOVA with repeated measures showed that there is an effect of the interaction time and group (F (2.12; 59.43) = 4.02; p < 0.05; ηp2 = 0.13) on the total score of the brief scale psychiatric assessment and neuropsychiatric inventory (F (1.58; 44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.

Conclusions: In this study, cannabidiol reduced psychological and behavioral symptoms in patients with vascular dementia. Future studies with larger samples are needed to confirm the findings. (F(1.58;44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.

Objectives: Despite the increasing number of people with dementia (PWD), detection remains low worldwide. In Brazil, PWD is expected to triple by 2050, and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of the under detection or characteristics of its distribution according to gender, age and region. We aimed to estimate the proportion of PWD not diagnosed in relation to the estimated number of PWD.

Methods: The number of diagnosed individuals were estimated based on national records of the prescription of anticholinesterases drugs (AChE) in 2022 for the treatment of mild and moderate stages of Alzheimer’s Disease (AD) held by the Unified Health System (SUS). Data were obtained from ftp://ftp.datasus.gov.br and drugs were dispensed according to the national clinical protocol. Studies from the national literature were consulted to estimate: (i) the number of people currently diagnosed with mild and moderate AD; (ii) the proportion of those who obtain AChE from SUS; (iii) the proportion of those who do not take AChE; and (iv) the proportion of AD related to other dementias. We assumed that the under-detection rate of AD would be similar to other dementias and 70% of the diagnosed AD individuals obtain AChE from SUS.

Results: More than 80% of the PWD 60+ are undetected (88.7%, 95% CI = 88.6–88.7). The poorest regions had higher rates (94.6% 95%, CI = 94.5–94.6) than the richest (84.8%, 95% CI = 84.7–84.8). Men had higher rates (89.8%, 95% CI = 89.7–89.9) than women (87.4%, 95% CI = 87.4–87.5). The youngest age group (60-64) had the highest rate (94.6%, 95% CI = 94.5–94.7) which decreased until 85–89 (84.3%, 95% CI = 84.2–84.4), before increasing again to 91.1% (95% CI = 91.0–91.2) among 90+.

Conclusions: Dementia under detection in Brazil is among the highest in the world. Fast populational aging and the highest rates among the youngest individuals are of concern as it may be related to late diagnosis. Gender and regional disparities also need to be considered when developing health policies.

Rotor-stator flows are known to exhibit instabilities in the form of circular and spiral rolls. While the spirals are known to emanate from a supercritical Hopf bifurcation, the origin of the circular rolls is still unclear. In the present work we suggest a quantitative scenario for the circular rolls as a response of the system to external forcing. We consider two types of axisymmetric forcing: bulk forcing (based on the resolvent analysis) and boundary forcing using direct numerical simulation. Using the singular value decomposition of the resolvent operator the optimal response is shown to take the form of circular rolls. The linear gain curve shows strong amplification at non-zero frequencies following a pseudo-resonance mechanism. The optimal energy gain is found to scale exponentially with the Reynolds number $Re$ (for $Re$ based on the rotation rate and interdisc spacing $H$). The results for both types of forcing are compared with former experimental works and previous numerical studies. Our findings suggest that the circular rolls observed experimentally are the effect of the high forcing gain together with the roll-like form of the leading response of the linearised operator. For high enough Reynolds number it is possible to delineate between linear and nonlinear responses. For sufficiently strong forcing amplitudes, the nonlinear response is consistent with the self-sustained states found recently for the unforced problem. The onset of such non-trivial dynamics is shown to correspond in state space to a deterministic leaky attractor, as in other subcritical wall-bounded shear flows.

The Prof pegmatite is located NW of Revelstoke, British Columbia, Canada on Boulder Mountain. Due to the abundance of petalite, the pegmatite is classified as a petalite subtype Li-Cs-Ta pegmatite or a Group one pegmatite. The Prof pegmatite contains a suite of minerals indicative of a highly evolved pegmatite melt including petalite, elbaite, lepidolite and Nb–Ta oxides. Four textural zones are present: (1) border; (2) intermediate, including (2.1) graphic texture dominant and (2.2) overgrowth dominant, where diverse minerals form rims around one another; (3) central; and (4) quartz. The border zone has a similar mineralogy to the intermediate zone and is interpreted to represent a chilled margin. The intermediate zone has a feldspar, mica, garnet and dravite–schorl dominant composition. The central zone hosts an evolved pegmatite core, which contains the majority of the lithium mineralisation composed of petalite, elbaite and lepidolite. The tourmaline, Nb–Ta oxides and mica within the pegmatite record the geochemical evolution of the melt from more primitive Fe- and Mg-rich minerals to a Li-, Mn- and Nb-rich assemblage indicative of a highly evolved geochemical system. The various pegmatitic textures and extremely fractionated geochemical composition of the pegmatite indicate that the melt was undercooled and crystallised rapidly. Three phases of metasomatism are recognised in the Prof pegmatite: an albitisation event observed cutting primary orthoclase; followed by a transition to a Na–Li–F-rich event mostly containing secondary albite, trilithionite and elbaites; and a sericitisation event.

The Prof pegmatite has a similar mineralogy to known pegmatites at Mount Begbie, 15 km to the south, in particular the notable presence of the rare mineral qitianlingite, petalite, lepidolite and elbaite. Together, these pegmatite bodies form part of an extensive, poorly mapped pegmatite field. Additional work is required to assess the extent and nature of mineralisation within this field.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.

Commentary of ‘Elemental psychopathology: distilling constituent symptoms and patterns of repetition in the diagnostic criteria of the DSM-5’ Vincent P. Martin 1, Régis Lopez 2,3, Jean-Arthur Micoulaud-Franchi 4,5, Christophe Gauld 4,6,*

GX is a code designed to solve the nonlinear gyrokinetic system for low-frequency turbulence in magnetized plasmas, particularly tokamaks and stellarators. In GX, our primary motivation and target is a fast gyrokinetic solver that can be used for fusion reactor design and optimization along with wide-ranging physics exploration. This has led to several code and algorithm design decisions, specifically chosen to prioritize time to solution. First, we have used a discretization algorithm that is pseudospectral in the entire phase space, including a Laguerre–Hermite pseudospectral formulation of velocity space, which allows for smooth interpolation between coarse gyrofluid-like resolutions and finer conventional gyrokinetic resolutions and efficient evaluation of a model collision operator. Additionally, we have built GX to natively target graphics processors (GPUs), which are among the fastest computational platforms available today. Finally, we have taken advantage of the reactor-relevant limit of small $\rho _*$ by using the radially local flux-tube approach. In this paper we present details about the gyrokinetic system and the numerical algorithms used in GX to solve the system. We then present several numerical benchmarks against established gyrokinetic codes in both tokamak and stellarator magnetic geometries to verify that GX correctly simulates gyrokinetic turbulence in the small $\rho _*$ limit. Moreover, we show that the convergence properties of the Laguerre–Hermite spectral velocity formulation are quite favourable for nonlinear problems of interest. Coupled with GPU acceleration, which we also investigate with scaling studies, this enables GX to be able to produce useful turbulence simulations in minutes on one (or a few) GPUs and higher fidelity results in a few hours using several GPUs. GX is open-source software that is ready for fusion reactor design studies.