We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Lyman alpha (Ly$\alpha$) forest in the spectra of $z\gt5$ quasars provides a powerful probe of the late stages of the epoch of reionisation (EoR). With the recent advent of exquisite datasets such as XQR-30, many models have struggled to reproduce the observed large-scale fluctuations in the Ly$\alpha$ opacity. Here we introduce a Bayesian analysis framework that forward-models large-scale lightcones of intergalactic medium (IGM) properties and accounts for unresolved sub-structure in the Ly$\alpha$ opacity by calibrating to higher-resolution hydrodynamic simulations. Our models directly connect physically intuitive galaxy properties with the corresponding IGM evolution, without having to tune ‘effective’ parameters or calibrate out the mean transmission. The forest data, in combination with UV luminosity functions and the CMB optical depth, are able to constrain global IGM properties at percent level precision in our fiducial model. Unlike many other works, we recover the forest observations without invoking a rapid drop in the ionising emissivity from $z\sim7$ to 5.5, which we attribute to our sub-grid model for recombinations. In this fiducial model, reionisation ends at $z=5.44\pm0.02$ and the EoR mid-point is at $z=7.7\pm0.1$. The ionising escape fraction increases towards faint galaxies, showing a mild redshift evolution at fixed UV magnitude, $M_\textrm{UV}$. Half of the ionising photons are provided by galaxies fainter than $M_\textrm{UV} \sim -12$, well below direct detection limits of optical/NIR instruments including $\textit{ JWST}$. We also show results from an alternative galaxy model that does not allow for a redshift evolution in the ionising escape fraction. Despite being decisively disfavoured by the Bayesian evidence, the posterior of this model is in qualitative agreement with that from our fiducial model. We caution, however, that our conclusions regarding the early stages of the EoR and which sources reionised the Universe are more model-dependent.
We determine the cones of effective and nef divisors on the toroidal compactification of the ball quotient model of the moduli space of complex cubic surfaces with a chosen line. From this we also compute the corresponding cones for the moduli space of unmarked cubic surfaces.
The incidence of facial palsy has been rising worldwide, with recent evidence emerging of links to COVID-19 infection. To date, guidance on cost-effective treatments is limited to medication (prednisolone). In terms of physical therapy, neuromuscular retraining (NMR) to restore balanced facial function has been most widely evaluated, but not in terms of cost effectiveness. The added value of telerehabilitation is unknown.
Methods
A multistage technology assessment was conducted, which included the following:
• a national survey of current therapy pathways in the UK and patients’ and clinicians’ views on the benefits and challenges of telerehabilitation;
• a systematic review of clinical effectiveness trials evaluating facial NMR therapy;
• calculation of long-term morbidity costs (national economic burden) based on incidence, patient recovery profiles, health-related quality of life, and national facial palsy treatment costs (valuation of clinical improvements in monetary terms was provided by a national Delphi panel); and
• evaluation of the cost effectiveness of telerehabilitation (remote monitoring wearables) added to current face-to-face NMR delivery.
Results
Nationally, approximately five percent of patients with facial palsy (17% of unresolved cases) are referred for facial NMR. The long-term economic burden associated with unresolved cases is estimated to range from GBP351 (EUR417) to GBP584 (EUR692) million, indicating substantial savings if long-term recovery can be improved. Medical treatment costs are GBP86.34 (EUR102) million per annual cohort, and physical and psychological therapy costs are GBP643,292 (EUR762,561). Economic modeling showed that telerehabilitation was cost effective, producing a health gain and a cost-saving of GBP468 (EUR555) per patient. If scaled to the national level for all patients who do not recover fully, an annual saving of GBP3.075 (EUR3.65) million is possible.
Conclusions
Economic modeling indicates that NMR could improve patient outcomes and reduce costs. The national survey demonstrated that access to NMR therapy services is limited, so introduction of telerehabilitation could improve access for currently underserved populations. Future clinical trials need to incorporate economic evaluations to help inform decision-making.
Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.
Globally, human rights violations experienced by persons with psychosocial, intellectual or cognitive disabilities continue to be a concern. The World Health Organization's (WHO) QualityRights initiative presents practical remedies to address these abuses. This paper presents an overview of the implementation of the initiative in Ghana.
Aims
The main objective of the QualityRights initiative in Ghana was to train and change attitudes among a wide range of stakeholders to promote recovery and respect for human rights for people with psychosocial, intellectual and cognitive disabilities.
Method
Reports of in-person and online training, minutes of meetings and correspondence among stakeholders of the QualityRights initiative in Ghana, including activities of international collaborators, were analysed to shed light on the implementation of the project in Ghana.
Results
In-person and online e-training on mental health were conducted. At the time of writing, 40 443 people had registered for the training, 25 416 had started the training and 20 865 people had completed the training and obtained a certificate. The team conducted 27 in-person training sessions with 910 people. The successful implementation of the project is underpinned by a committed partnership among stakeholders, strong leadership from the coordinating agency, the acceptance of the initiative and the outcome. A few challenges, both in implementation and acceptance, are discussed.
Conclusions
The exposure of the WHO QualityRights initiative to a substantial number of key stakeholders involved in mental healthcare in Ghana is critical to reducing human rights abuses for people with psychosocial, intellectual and cognitive disabilities.
Fetuses undergo major surgical stress as well as fluid shifts secondary to both twin-twin transfusion (TTTS) as well as the fetoscopic surgery for treatment of TTTS. While the pathophysiology of TTTS is understood, the acute metabolic changes that fetuses experience from fetoscopic surgery are not. We sought to evaluate the changes in recipient metabolomic profile secondary to TTTS surgery. Amniotic fluid was collected at the beginning and end of four TTTS surgical cases performed from 12/2022−2/2023. Samples were immediately processed and evaluated via NMR-based Metabolomics Facility protocol. In univariate analysis, 12 metabolites (glucose, lactate, and 10 key amino acids) showed statistically significant changes between the beginning and end of the surgery. Among these, 11 metabolites decreased at the end, while only lactate increased. Supervised oPLS-DA modeling revealed pyruvate and lactate as the two metabolites most impact on the variance between cases, and that 40% of metabolomic changes could be attributed directly to the timing that the sample was taken (i.e., if pre- or postoperatively). These results indicate significant metabolic changes in the recipient twin during fetoscopic surgery for TTTS. These findings of decreased glucose, increased lactate, and decreased amnio acids would indicate increased catabolism during surgery. This study raises questions regarding optimal maternal and fetal nutrition during surgery and if nutritional status could be optimized to further improve twin survival during fetoscopic surgery.
The well-studied moduli space of complex cubic surfaces has three different, but isomorphic, compact realizations: as a GIT quotient ${\mathcal {M}}^{\operatorname {GIT}}$, as a Baily–Borel compactification of a ball quotient ${(\mathcal {B}_4/\Gamma )^*}$, and as a compactified K-moduli space. From all three perspectives, there is a unique boundary point corresponding to non-stable surfaces. From the GIT point of view, to deal with this point, it is natural to consider the Kirwan blowup ${\mathcal {M}}^{\operatorname {K}}\rightarrow {\mathcal {M}}^{\operatorname {GIT}}$, whereas from the ball quotient point of view, it is natural to consider the toroidal compactification ${\overline {\mathcal {B}_4/\Gamma }}\rightarrow {(\mathcal {B}_4/\Gamma )^*}$. The spaces ${\mathcal {M}}^{\operatorname {K}}$ and ${\overline {\mathcal {B}_4/\Gamma }}$ have the same cohomology, and it is therefore natural to ask whether they are isomorphic. Here, we show that this is in fact not the case. Indeed, we show the more refined statement that ${\mathcal {M}}^{\operatorname {K}}$ and ${\overline {\mathcal {B}_4/\Gamma }}$ are equivalent in the Grothendieck ring, but not K-equivalent. Along the way, we establish a number of results and techniques for dealing with singularities and canonical classes of Kirwan blowups and toroidal compactifications of ball quotients.
Treatment of seriously ill patients is often complicated by prolonged or complex transfers between hospitals in sub-Saharan Africa. Difficulties or inefficiency in these transfers can lead to poor outcomes for patients. “On-call” triage systems have been utilized to facilitate communication between facilities and to avoid poor outcomes associated with patient transfer. This study attempts to examine the effects of a pilot study to implement such a system in Rwanda.
Methods:
Data collection occurred prospectively in two stages, pre-intervention and intervention, in the emergency department (ED) at Kigali University Teaching Hospital (CHUK). All patients transferred during the pre-determined timeframe were enrolled. Data were collected by ED research staff via a standardized form. Statistical analysis was performed using STATA version 15.0. Differences in characteristics were assessed using χ2 or Fisher’s exact tests for categorical variables and independent sample t-tests for normally distributed continuous variables.
Results:
During the “on call” physician intervention, the indication for transfer was significantly more likely to be for critical care (P <.001), transfer times were faster (P <.001), patients were more likely to be displaying emergency signs (P <.001), and vital signs were more likely to be collected prior to transport (P <.001) when compared to the pre-interventional phase.
Conclusion:
The “[Emergency Medicine] EM Doc On Call” intervention was associated with improved timely interhospital transfer and clinical documentation in Rwanda. While these data are not definitive due to multiple limitations, it is extremely promising and worthy of further study.
Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.
Methods
Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).
Results
The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.
Conclusions
Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.
Inaccurate representations of iceberg calving from ice shelves are a large source of uncertainty in mass-loss projections from the Antarctic ice sheet. Here, we address this limitation by implementing and testing a continuum damage-mechanics model in a continental scale ice-sheet model. The damage-mechanics formulation, based on a linear stability analysis and subsequent long-wavelength approximation of crevasses that evolve in a viscous medium, links damage evolution to climate forcing and the large-scale stresses within an ice shelf. We incorporate this model into the BISICLES ice-sheet model and test it by applying it to idealized (1) ice tongues, for which we present analytical solutions and (2) buttressed ice-shelf geometries. Our simulations show that the model reproduces the large disparity in lengths of ice shelves with geometries and melt rates broadly similar to those of four Antarctic ice shelves: Erebus Glacier Tongue (length ~ 13 km), the unembayed portion of Drygalski Ice Tongue (~ 65 km), the Amery Ice Shelf (~ 350 km) and the Ross Ice Shelf (~ 500 km). These results demonstrate that our simple continuum model holds promise for constraining realistic ice-shelf extents in large-scale ice-sheet models in a computationally tractable manner.
Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming.
Design:
Longitudinal follow-up of a birth cohort.
Setting:
CSI Holdsworth Memorial Hospital (HMH), Mysore South India.
Participants:
721 men and women (55–80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life.
Measurements:
Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders
Results:
Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants’ own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors and was attenuated after adjustment for all lifecourse factors (0.08 SD per SD birth weight [95% CI −0.01, 0.18] p = 0.07).
Conclusions:
The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.
Biofortified yellow cassava has been developed to alleviate vitamin A deficiency. We examined the potential contribution of yellow cassava to total retinol activity equivalent (RAE) intake if replacing white by yellow cassava among pre-school Nigerian children. Dietary intake was assessed as part of a randomised controlled trial. Pre-schoolchildren (n 176) were randomly assigned to receive either white cassava (WC) or yellow cassava (YC) for 17 weeks. Dietary intake assessments were conducted during the intervention and 1 month after, when children had resumed their habitual diet. Differences in RAE intake between groups and time points were compared using a linear mixed model regression analysis. During intervention, median RAE intake was 536 µg/d in the YC group and 301 µg/d in the WC group (P < 0·0001). YC contributed approximately 40 % to total RAE intake. Of the children, 9 % in the YC group and 29 % in the WC group had RAE intake below the Estimated Average Requirement. After intervention, median RAE intake was 300 µg/d and did not differ between intervention groups (P = 0·5). The interaction effect of group and time showed a 37 % decrease in RAE intake in the YC group after the intervention (Exp(β) = 0·63; 95 % CI 0·56, 0·72). If WC was replaced by YC after intervention, the potential contribution of YC to total RAE intake was estimated to be approximately 32 %. YC increased total RAE intake and showed a substantially lower inadequacy of intake. It is therefore recommended as a good source of provitamin A in cassava-consuming regions.
This Element describes for the first time the database of peer review reports at PLOS ONE, the largest scientific journal in the world, to which the authors had unique access. Specifically, this Element presents the background contexts and histories of peer review, the data-handling sensitivities of this type of research, the typical properties of reports in the journal to which the authors had access, a taxonomy of the reports, and their sentiment arcs. This unique work thereby yields a compelling and unprecedented set of insights into the evolving state of peer review in the twenty-first century, at a crucial political moment for the transformation of science. It also, though, presents a study in radicalism and the ways in which PLOS's vision for science can be said to have effected change in the ultra-conservative contemporary university. This title is also available as Open Access on Cambridge Core.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
To develop a semi-quantitative FFQ and to evaluate its validity and reproducibility for the assessment of total dietary intake of Kenyan urban adult population, given its non-existence in Kenya.
Design:
The current study adopted a cross-sectional design. A culture-sensitive semi-quantitative FFQ was developed and its validity was tested relative to three non-consecutive 24-h recalls (24hR). Reproducibility was tested by the test–retest method, with a 3-week interval. Spearman’s correlation coefficients and intra-class correlation coefficients were calculated for several macro- and micronutrients. Cross-classification into quartiles and Bland and Altman plots were analysed.
Setting:
Nairobi county (Dagoreti South and Starehe constituencies).
Participants:
A convenient sample was recruited in three different clusters in Nairobi.
Results:
A culture-sensitive 123-food-item semi-quantitative FFQ showed higher nutrient intakes compared with the 24hR (total energy median 12543·632 v. 8501·888 kJ, P < 0·001). Energy-adjusted and deattenuated Spearman’s correlations for macronutrients ranged between 0·21 (total fat) and 0·47 (protein). The agreement in the same quartile varied from 28 % (protein) to 41 % (carbohydrates). Including adjacent quartiles, the range increased: 76 % (protein and fat) to 81 % (carbohydrates). The extreme disagreement was low. The first FFQ application resulted in higher mean values for all nutrients compared with the second FFQ (total energy median 12459·952 v. 10485·104 kJ, P < 0·001). Energy-adjusted correlations for macronutrients ranged from 0·28 (carbohydrates) to 0·61 (protein). Intra-class correlation coefficients for macronutrients were moderate, between 0·6 and 0·7.
Conclusions:
The developed semi-quantitative FFQ was shown to be a valid and reproducible tool for ranking urban adult Kenyans according to their dietary intake.