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Malacological surveys were conducted in 2021 in the Kimpese region of Central Kongo Province, west of the Democratic Republic of Congo (DRC). Snail specimens were collected following a standardised protocol, identified using morphological and molecular methods, and tested for schistosome infection using a diagnostic PCR assay. Positive snail samples were sequenced to characterise the infecting schistosome species. Partial mitochondrial cytochrome c oxidase subunit 1 (COX1) gene sequences were used in phylogenetic analyses to explore the evolutionary position of these snail species within the broader African context. At least four intermediate snail hosts were identified: Bulinus truncatus, Bulinus forskalii, Biomphalaria pfeifferi, and a Biomphalaria species belonging to the Nilotic species complex (tentatively named Biomphalaria cf sudanica), of which the species identity needs to be confirmed. A total of 37 out of 1,196 snails (3.1%) tested positive for schistosome infection, with an infection prevalence of 7.4% for B. truncatus with Schistosoma haematobium and 1.5% for Biomphalaria spp. with Schistosoma mansoni. The S. mansoni sequence retrieved from these samples formed a basal clade relative to Zambian isolates, whereas S. haematobium grouped with the most frequently characterised haplotype cluster previously identified across mainland Africa. It is important to note that no animal schistosome species were identified in this study. Both the sequences from the snail hosts and the parasites represent novel contributions from the DRC. Additionally, the findings update the current knowledge of schistosomiasis transmission in the Kimpese region by providing insight into the phylogenetic placement, species diversity, and infection status of local snail populations.
Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.
There is growing evidence that smoking increases the risk of developing psychiatric disorders, but the underlying mechanisms are largely unknown. We examine brain structure as a potential pathway between smoking and psychiatric disease liability.
Methods
We test associations between smoking (initiation, cigarettes per day, cessation, lifetime use) and depression, bipolar disorder, and schizophrenia, with and without correcting for volume of the amygdala, hippocampus, lateral and medial orbitofrontal cortex, superior frontal context, and cortical thickness and surface area. We use three methods that use summary statistics of genome-wide association studies to investigate genome-wide and local genetic overlap (genomic structural equation modeling, local analysis of (co)variant association), as well as causal associations (Mendelian randomization).
Results
While we find causal effects of smoking on brain volume in different brain areas, and with psychiatric disorders, brain volume did not seem to mediate the effect of smoking on psychiatric disorders.
Conclusions
While these findings are limited by characteristics of the included summary statistics (e.g. sample size), we conclude that brain volume of these areas is unlikely to explain a substantial part of any effect of smoking on psychiatric disorders. Nevertheless, genetic methods are valuable tools for exploring other potential mechanisms, such as brain functional connectivity, foregoing the need to collect all phenotypes in one dataset.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
The number of people affected by at least one chronic disease is increasing worldwide, with poorer health-related quality of life (HRQOL) being a major consequence(1). HRQOL is an important measure for quantifying and evaluating the impacts of a disease or intervention on self-perceived wellbeing. Anti-inflammatory diets are consistently associated with improvements in disease-specific outcomes(2,3), but their effect on HRQOL is unclear. This systematic review and meta-analysis aimed to estimate the effectiveness of anti-inflammatory dietary interventions on HRQOL in adults with one or more chronic diseases. Five databases were searched from inception to May 2024 for randomised controlled trials evaluating the impact of an anti-inflammatory diet (e.g., Mediterranean, low-carbohydrate) on HRQOL. Screening, data extraction, and risk of bias assessment using the Cochrane Risk of Bias v2.0 tool were performed independently by two authors. Certainty of evidence was determined using the GRADE approach. Pooled effect sizes for HRQOL, separated into mental (MCS) physical (PCS) and general component scores (GCS) were calculated using random-effects meta-analyses and reported as standardised mean difference (SMD). Subgroup analyses and meta-regressions were performed to assess the influence of study-level characteristics on HRQOL outcomes. Twenty-three studies reporting HRQOL data for 2753 participants were included. The most common chronic diseases evaluated were type 2 diabetes (8 studies, 35%), musculoskeletal conditions (5 studies, 22%), and cardiovascular conditions (3 studies, 13%). Anti-inflammatory dietary interventions evaluated included the Mediterranean diet (14 studies, 61%), low-carbohydrate diets (8 studies, 35%), Dietary Approaches to Stop Hypertension (1 study, 4%) and low-sugar, low-yeast diet (1 study, 4%). Anti-inflammatory diets were associated with small improvements in PCS compared to usual care/non-anti-inflammatory dietary interventions such as national dietary guidelines and low-fat diets (SMD 0.22, 95% CI 0.06 to 0.38) but not MCS (SMD 0.10, 95% CI −0.02 to 0.23) or GCS (SMD 0.40, 95% CI −0.32 to 1.13). Assessment by study-level characteristics revealed that studies with a higher risk of bias reported a larger effect on PCS, and diet-only interventions (compared to multi-component interventions) had a greater effect on MCS. No study met the Cochrane criteria for low risk of bias, and certainty of evidence was low (PCS and MCS) to very low (GCS). This systematic review suggests that anti-inflammatory diets may lead to a small improvement in physical HRQOL, but not mental or general HRQOL. The low certainty of evidence calls for further high-quality RCTs with detailed descriptions of dietary interventions in individuals with one or more chronic diseases.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Since cannabis was legalized in Canada in 2018, its use among older adults has increased. Although cannabis may exacerbate cognitive impairment, there are few studies on its use among older adults being evaluated for cognitive disorders.
Methods:
We analyzed data from 238 patients who attended a cognitive clinic between 2019 and 2023 and provided data on cannabis use. Health professionals collected information using a standardized case report form.
Results:
Cannabis use was reported by 23 out of 238 patients (9.7%): 12 took cannabis for recreation, 8 for medicinal purposes and 3 for both purposes. Compared to non-users, cannabis users were younger (mean ± SD 62.0 ± 7.5 vs 68.9 ± 9.5 years; p = 0.001), more likely to have a mood disorder (p < 0.05) and be current or former cigarette smokers (p < 0.05). There were no significant differences in sex, race or education. The proportion with dementia compared with pre-dementia cognitive states did not differ significantly in users compared with non-users. Cognitive test scores were similar in users compared with non-users (Montreal Cognitive Assessment: 20.4 ± 5.0 vs 20.7 ± 4.5, p = 0.81; Folstein Mini-Mental Status Exam: 24.5 ± 5.1 vs 26.0 ± 3.6, p = 0.25). The prevalence of insomnia, obstructive sleep apnea, anxiety disorders, alcohol use or psychotic disorders did not differ significantly.
Conclusion:
The prevalence of cannabis use among patients with cognitive concerns in this study was similar to the general Canadian population aged 65 and older. Further research is necessary to investigate patients’ motivations for use and explore the relationship between cannabis use and mood disorders and cognitive decline.
We report a set of radiocarbon dating of prehistoric settlements located on the paleolake Baruun Khuree shores in the Gobi-Altai area, southern Mongolia. The obtained series of 11 AMS 14C measurements on charcoal and other charred plant macro-remains can be associated with one of the earliest episodes of the Holocene highly mobile desert-adapted hunter-gatherers activities from the Gobi desert (ca. 11,250–10,500 cal BP). Exploiting a wide range of environments, including dune fields, they are characterized by pottery usage and microblade core technology with wedge-shaped cores as well as osteological materials. These preliminary results are part of a project analyzing the nature of long-lasting prehistoric occupation around Tsakhiurtyn Hundi (Eng. Flint Valley)—one of the most extensive early prehistoric sites of Central Asia owing its name to the presence of abundant flint outcrops, lithic workshops and their innumerable flint artifacts.
We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.
In this work, we present a detailed assessment of fusion-born alpha-particle confinement, their wall loads and stability of Alfvén eigenmodes driven by these energetic particles in the Infinity Two Fusion Pilot Plant baseline plasma design, a four-field-period quasi-isodynamic stellarator to operate in deuterium–tritium fusion conditions. Using the Monte Carlo codes, SIMPLE, ASCOT5 and KORC-T, we study the collisionless and collisional dynamics of guiding-centre and full-orbit alpha-particles in the core plasma. We find that core energy losses to the wall are less than 4 %. Our simulations shows that peak power loads on the wall of this configuration are approximately 2.5 MW m-$^2$ and are spatially localised, toroidally and poloidaly, in the vicinity of x-points of the magnetic island chain $n/m = 4/5$ outside the plasma volume. Also, an exploratory analysis using various simplified walls shows that shaping and distance of the wall from the plasma volume can help reduce peak power loads. Our stability assessment of Alfvén eigenmodes using the STELLGAP and FAR3d codes shows the absence of unstable modes driven by alpha-particles in Infinity Two due to the relatively low alpha-particle beta at the envisioned 800 MW operating scenario.
The magnetohydrodynamic (MHD) equilibrium and stability properties of the Infinity Two fusion pilot plant baseline plasma physics design are presented. The configuration is a four-field period, aspect ratio $A = 10$ quasi-isodynamic stellarator optimised for excellent confinement at elevated density and high magnetic field $B = 9\,T$. Magnetic surfaces exist in the plasma core in vacuum and retain good equilibrium surface integrity from vacuum to an operational $\beta = 1.6 \,\%$, the ratio of the volume average of the plasma and magnetic pressures, corresponding to $800\ \textrm{MW}$ deuterium–tritium fusion operation. Neoclassical calculations show that a self-consistent bootstrap current of the order of ${\sim} 1\ \textrm{kA}$ slightly increases the rotational transform profile by less than 0.001. The configuration has a magnetic well across its entire radius. From vacuum to the operating point, the configuration exhibits good ballooning stability characteristics, exhibits good Mercier stability across most of its minor radius and it is stable against global low-n MHD instabilities up to $\beta = 3.2\,\%$.
Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.
This study introduces the prostate cancer linear energy transfer sensitivity index (PCLSI) as a novel method to predict relative biological effectiveness (RBE) in prostate cancer using linear energy transfer (LET) in proton therapy based on screening for DNA repair mutations.
Materials and Methods:
Five prostate cancer cell lines with DNA repair mutations known to cause sensitivity to LET and DNA repair inhibitors were examined using published data. Relative Du145 LET sensitivity data were leveraged to deduce the LET equivalent of olaparib doses. The PCLSI model was built using three of the prostate cancer cell lines (LNCaP, 22Rv1 and Du145) with DNA mutation frequency from patient cohorts. The PCLSI model was compared against two established RBE models, McNamara and McMahon, for LET-optimized prostate cancer treatment plans.
Results:
The PCLSI model relies on the presence of eight DNA repair mutations: AR, ATM, BRCA1, BRCA2, CDH1, ETV1, PTEN and TP53, which are most likely to predict increased LET sensitivity and RBE in proton therapy. In the LET-optimized plan, the PCLSI model indicates that prostate cancer cells with these DNA repair mutations are more sensitive to increased LET than the McNamara and McMahon RBE models, with expected RBE increases ranging from 11%–33% at 2keV/µm.
Conclusions:
The PCLSI model predicts increasing RBE as a function of LET in the presence of certain genetic mutations. The integration of LET-optimized proton therapy and genetic mutation profiling could be a significant step toward the use of individualized medicine to improve outcomes using RBE escalation without the potential toxicity of physical dose escalation.
Traditional wavefront control in high-energy, high-intensity laser systems usually lacks real-time capability, failing to address dynamic aberrations. This limits experimental accuracy due to shot-to-shot fluctuations and necessitates long cool-down phases to mitigate thermal effects, particularly as higher repetition rates become essential, for example, in inertial fusion research. This paper details the development and implementation of a real-time capable adaptive optics system at the Apollon laser facility. Inspired by astronomical adaptive optics, the system uses a fiber-coupled 905 nm laser diode as a pilot beam that allows for spectral separation, bypassing the constraints of pulsed lasers. A graphics processing unit-based controller, built on the open-source Compute And Control for Adaptive Optics framework, manages a loop comprising a bimorph deformable mirror and a high-speed Shack–Hartmann sensor. Initial tests showed excellent stability and effective aberration correction. However, integration into the Apollon laser revealed critical challenges unique to the laser environment that must be resolved to ensure safe operation with amplified shots.
Maize (Zea mays L.) is one of the main staples in the Peruvian Andes. Phenotypic diversity is extremely high in terms of plant morphology, grain colour, grain size and uses. However, little is known about the genetic component of the Peruvian maize. Genotyping-by-sequencing was used, for the first time, to infer the genetic diversity and population structure of 25 accessions of maize collected from two ecoregions of the departments of the Peruvian highlands, Cajamarca and Huancavelica, to provide a basis for the conservation and breeding of this crop genetic resource. A total of 29,332 single-nucleotide polymorphisms were identified along all 10 chromosomes of maize. STRUCTURE analysis revealed two clusters (open-pollinated cultivars and landraces). Principal coordinate analysis and our dendrogram showed that these accessions of Peruvian maize do not group based on their geographic origin but on their improvement status, however, this is weakly supported. Average genetic diversity was very high (0.35). Analysis of molecular variance showed a reduced variation between populations (2.85%) and indicated that variability within populations is 97.15%. The lowest population divergence was zero for populations of Colcabamba versus Pichos and Daniel Hernandez versus Colcabamba and the highest population divergence (0.041) was observed for population Cajamarca versus Santiago de Tucuma. As expected, FIS values were positive. Additional samples from other Andean and west coast Peruvian localities are needed to provide a better understanding of the genetic components of this important crop aiming to develop a modern breeding programme of maize in Peru.
Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.