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Heath forests, or known locally as kerangas, in Indonesia and Malaysia form a distinct and understudied ecoregion. We document the distribution and ecological significance of the largest extent of kerangas in Kalimantan, Indonesian Borneo. We mapped 16,586 km2 of kerangas to the nearest one square kilometre across Kalimantan, showing a significant reduction from previous estimates. About 19% of this area exists as a poorly documented mosaic landscape in Central Kalimantan’s Rungan-Kahayan region. Here, peat-based forests transition to heath and dipterocarp forests, making it difficult to reliably classify these forests for conservation planning. Using remote sensing and tree plot data, we identified three forest types—kerangas, low pole, and mixed swamp. Vegetation structure is influenced by soil, topography, and hydrology, while peat depth and elevation affect species diversity. Our findings indicate that these forests are dynamic ecosystems with diverse vegetation communities adapted to peat as well as sandy soils. Lowland heath forests in Rungan-Kahayan exhibits higher tree densities compared to other Bornean heath forests, reflecting unique ecological adaptations to challenging environments. Despite covering just 3% of Kalimantan’s forest area, these ecosystems remain largely unprotected, facing threats from land conversion and fire. Our study highlights the ecological complexity of kerangas and underscores the urgent need for targeted conservation and further research on these forests.
The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Haemolysis is developing prominence in the setting of supporting increasingly complex children with heart failure with a ventricular assist device. The goal of this study is to better characterise haemolysis and its implications in children supported with pulsatile ventricular assist devices.
Methods:
This is a single-centre retrospective review of 44 children who were supported by Berlin Heart EXCOR between January 2006 and June 2020. Patients were divided into major haemolysers and non-major haemolysers. Major haemolysers were defined as patients with lactate dehydrogenase > 500U/L (2.5x the upper limits of normal) with either total bilirubin > 2mg/dL (with predominantly indirect hyperbilirubinemia) or anaemia out of proportion to the clinical scenario more than three days following implantation of the ventricular assist device(s). Patient demographics, ventricular assist device factors, and outcomes, including end-organ function and mortality, were compared between major haemolysers and non-major haemolysers.
Main results:
Forty-four patients supported by the Berlin EXCOR were included in the analytic cohort of the study: 27 major haemolysers and 17 non-major haemolysers. Major haemolysis was more common in those supported with single-ventricle ventricular assist device (i.e., VAD in the context of functionally univentricular anatomy) compared to those with biventricular hearts, p = 0.01. There were no patients with an isolated left ventricular assist device or isolated right ventricular assist device in our analytic cohort of 44 patients. Of the 19 patients with single-ventricle ventricular assist device, 84% (16/19) were major haemolysers. Of the 25 patients with a biventricular assist device, 44% (11/25) were major haemolysers. Major haemolysers and non-major haemolysers had a body surface area of 0.28 and 0.40, respectively (p = 0.01). Overall, survival to discharge from the hospital was 66% (n = 29/44). Survival to discharge from the hospital was 52% (14/27) in major haemolysers versus 88% (15/17) in non-major haemolysers, p = 0.02. Only 3 of the 27 with major haemolysis had severe haemolysis, that is, lactate dehydrogenase > 2000 and bilirubin above 10. Non-major haemolysers had a better improvement in creatinine clearance during ventricular assist device support, p < 0.0001. (During the same era of this study, 22 patients who were supported with Berlin Heart were excluded from the analytic cohort because they did not have any recorded measurement of lactate dehydrogenase. Seventeen of these 22 patients had no clinical evidence of haemolysis. Survival to discharge from the hospital in this excluded cohort was 86% [19/22].)
Conclusions:
Major haemolysis in patients with pulsatile ventricular assist device is more likely with single-ventricle ventricular assist device support and smaller body surface area.
Threat sensitivity, an individual difference construct reflecting variation in responsiveness to threats of various types, predicts physiological reactivity to aversive stimuli and shares heritable variance with anxiety disorders in adults. However, no research has been conducted yet with youth to examine the heritability of threat sensitivity or evaluate the role of genetic versus environmental influences in its relations with mental health problems. The current study addressed this gap by evaluating the psychometric properties of a measure of this construct, the 20-item Trait Fear scale (TF-20), and examining its phenotypic and genotypic correlations with different forms of psychopathology in a sample of 346 twin pairs (121 monozygotic), aged 9–14 years. Analyses revealed high internal consistency and test-retest reliability for the TF-20. Evidence was also found for its convergent and discriminant validity in terms of phenotypic and genotypic correlations with measures of fear-related psychopathology. By contrast, the TF-20’s associations with depressive conditions were largely attributable to environmental influences. Extending prior work with adults, current study findings provide support for threat sensitivity as a genetically-influenced liability for phobic fear disorders in youth.
Increased antibiotic use (AU) has been reported globally during the COVID-19 pandemic despite low rates of bacterial co-infection. We assessed changes in AU during the COVID-19 pandemic in Indonesia and the Philippines.
Methods:
We evaluated hospital-wide AU over 36 months in six hospitals, 3 in Indonesia and 3 in the Philippines. Intravenous antibiotics commonly used for respiratory conditions were selected and grouped for analysis. AU rates were calculated as monthly defined daily dose per 1000 patient-days or patient discharges. Median AU rates were compared from the pre-pandemic (March 2018–February 2020) and pandemic periods (March 2020–February 2021) using quantile regression to assess for statistical significance. Changes in AU during the COVID-19 pandemic were analyzed using interrupted time series analysis.
Results:
Significant increases were noted in the median AU rate from the pre-pandemic to pandemic period of all antibiotics combined in 3/6 hospitals (percentage change, Δ, 12.5%–63.6%) and anti-pseudomonal antibiotics in 3/6 hospitals (Δ 51.5%–161.5%). In the interrupted time series analysis, an immediate increase (range: 125.40–1762) in the use of all included antibiotics combined was observed in 3/6 hospitals at the onset of the COVID-19 pandemic. One of these 3 hospitals experienced a statistically significant sustained increase, while another experienced a decrease over time.
Conclusions:
We observed significant increases in facility-wide inpatient AU during the COVID-19 pandemic in our participating hospitals in Indonesia and the Philippines. These findings reinforce the importance of antibiotic stewardship practices to optimize AU, especially during infectious disease pandemics.
This study evaluated the impact of four cover crop species and their termination timings on cover crop biomass, weed control, and corn yield. A field experiment was arranged in a split-plot design in which cover crop species (wheat, cereal rye, hairy vetch, and rapeseed) were the main plot factor, and termination timings [4, 2, 1, and 0 wk before planting corn (WBP)] was the subplot factor. In both years (2021 and 2022), hairy vetch produced the most biomass (5,021 kg ha–1) among cover crop species, followed by cereal rye (4,387 kg ha–1), wheat (3,876 kg ha–1), and rapeseed (2,575 kg ha–1). Regression analysis of cover crop biomass with accumulated growing degree days (AGDDs) indicated that for every 100 AGDD increase, the biomass of cereal rye, wheat, hairy vetch, and rapeseed increased by 880, 670, 780, and 620 kg ha–1, respectively. The density of grass and small-seeded broadleaf (SSB) weeds at 4 wk after preemergence herbicide (WAPR) application varied significantly across termination timings. The grass and SSB weed densities were 56% and 36% less at 0 WBP compared with 2 WBP, and 67% and 61% less compared with 4 WBP. The sole use of a roller-crimper did not affect the termination of rapeseed at 0 WBP and resulted in the least corn yield (3,046 kg ha–1), whereas several different combinations of cover crops and termination timings resulted in greater corn yield. In conclusion, allowing cover crops to grow longer in the spring offers more biomass for weed suppression and impacts corn yield.
Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.
The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.
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.
Despite a rich literature on the determinants of democracy, the influence of one theoretically important factor has been neglected thus far. Unlike factors such as development, growth, and inequality, the concentration of economic power and its correlate, business unity, have not received systematic empirical treatment. We argue that this factor may act as a deterrent to democracy. Using a dataset covering 120 countries over 23 years, from 1988 through 2010, we find evidence for a negative effect of economic concentration on a nation’s level of democracy. We also show evidence suggesting that corporate political activity may provide a mechanism through which this negative effect is exercised. Our results point to the need to further understand the processes through which business elites undermine democracy.
Many studies argue that the World Bank grants favorable loan conditions to allies of its powerful principals. These studies typically use the count of conditions as a proxy for how demanding loans are on borrowers, even though some conditions are more difficult to comply with than others. We propose a new operationalization: a measure of conditionality stringency in Bank loans constructed using Latent Semantic Scaling. Using this new measure, we find little evidence of a generalizable influence of powerful principals. Instead, the stringency of loan conditions is associated with bureaucratic assessments of risk. To facilitate future research, we provide a new dataset of World Bank loan condition texts and our measure of text stringency for all loans in the dataset.
This volume offers an overview of the state of the field, and shows the importance of Islamic inscriptions for disciplines such as art history, history and literature. The chapters range from surveys to detailed exploration of individual topics, providing an insight to some of the most recent cutting-edge work on Islamic inscriptions. It focuses on the period from the rise of Islam to the fifteenth century, ranging across the Islamic world from the Maghreb to India and Central Asia, and inscriptions in Arabic, Persian and Turkish.
The five sections of the book draw together some of the principal themes: 'Royal Power' investigates the role of sultanic patronage in epigraphy, and the use of inscriptions for projecting royal power. 'Piety' examines the relationship between epigraphy and religious practice. 'Epigraphic Style and Function' explores the relationship between the use of specific epigraphic styles and scripts and the function of a monument. 'Inscribed Objects' moves from monumental inscriptions to those on objects such as ceramics and pen-cases. The final section considers the interplay between inscriptions and historical sources as well as the utility of inscriptions as historical sources.
Limited access to multiple sclerosis (MS)-focused care in rural areas can decrease the quality of life in individuals living with MS while influencing both physical and mental health.
Methods:
The objectives of this research were to compare demographic and clinical outcomes in participants with MS who reside within urban, semi-urban and rural settings within Newfoundland and Labrador. All participants were assessed by an MS neurologist, and data collection included participants’ clinical history, date of diagnosis, disease-modifying therapy (DMT) use, measures of disability, fatigue, pain, heat sensitivity, depression, anxiety and disease activity.
Results:
Overall, no demographic differences were observed between rural and urban areas. Furthermore, the categorization of primary residence did not demonstrate any differences in physical disability or indicators of disease activity. A significantly higher percentage of participants were prescribed platform or high-efficacy DMTs in semi-urban areas; a higher percentage of participants in urban and rural areas were prescribed moderate-efficacy DMTs. Compared to depression, anxiety was more prevalent within the entire cohort. Comparable levels of anxiety were measured across all areas, yet individuals in rural settings experienced greater levels of depression. Individuals living with MS in either an urban or rural setting demonstrated clinical similarities, which were relatively equally managed by DMTs.
Conclusion:
Despite greater levels of depression in rural areas, the results of this study highlight that an overall comparable level and continuity of care is provided to individuals living with MS within rural and urban Newfoundland and Labrador.
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.
Partial remission after major depressive disorder (MDD) is common and a robust predictor of relapse. However, it remains unclear to which extent preventive psychological interventions reduce depressive symptomatology and relapse risk after partial remission. We aimed to identify variables predicting relapse and to determine whether, and for whom, psychological interventions are effective in preventing relapse, reducing (residual) depressive symptoms, and increasing quality of life among individuals in partial remission. This preregistered (CRD42023463468) systematic review and individual participant data meta-analysis (IPD-MA) pooled data from 16 randomized controlled trials (n = 705 partial remitters) comparing psychological interventions to control conditions, using 1- and 2-stage IPD-MA. Among partial remitters, baseline clinician-rated depressive symptoms (p = .005) and prior episodes (p = .012) predicted relapse. Psychological interventions were associated with reduced relapse risk over 12 months (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43–0.84), and significantly lowered posttreatment depressive symptoms (Hedges’ g = 0.29, 95% CI 0.04–0.54), with sustained effects at 60 weeks (Hedges’ g = 0.33, 95% CI 0.06–0.59), compared to nonpsychological interventions. However, interventions did not significantly improve quality of life at 60 weeks (Hedges’ g = 0.26, 95% CI -0.06 to 0.58). No moderators of relapse prevention efficacy were found. Men, older individuals, and those with higher baseline symptom severity experienced greater reductions in symptomatology at 60 weeks. Psychological interventions for individuals with partially remitted depression reduce relapse risk and residual symptomatology, with efficacy generalizing across patient characteristics and treatment types. This suggests that psychological interventions are a recommended treatment option for this patient population.
The aardvark (Oryecteropus afer) is a fossorial species with a widespread distribution across sub-Saharan Africa. It leaves distinctive tracks and traces of its presence, including large burrows. However, despite a substantial body fossil record, few trace fossils registered by aardvarks have been described. Its distribution range in southern Africa during historic and prehistoric times was probably broadly similar to that of today, with the addition of the currently submerged Palaeo-Agulhas Plain during much of the Pleistocene. Five new trace fossil sites have been identified in Pleistocene aeolianites on the Cape coast and are here interpreted with varying degrees of confidence as large burrows that were made by aardvarks. In addition, a possible aardvark tracksite has been identified. Together these add to the sparse paleoichnological evidence of aardvarks and add to the global ichnological record of large vertebrate burrows. While at this point the evidence does not warrant the proposal of new ichnotaxa, the findings may act to spur further identification of fossilized traces of aardvarks and other fossorial species on the Cape coast and beyond.
We discuss the emerging technology of digital twins (DTs) and the expected demands as they scale to represent increasingly complex, interconnected systems. Several examples are presented to illustrate core use cases, highlighting a progression to represent both natural and engineered systems. The forthcoming challenges are discussed around a hierarchy of scales, which recognises systems of increasing aggregation. Broad implications are discussed, encompassing sensing, modelling, and deployment, alongside ethical and privacy concerns. Importantly, we endorse a modular and peer-to-peer view for aggregate (interconnected) DTs. This mindset emphasises that DT complexity emerges from the framework of connections (Wagg et al. [2024, The philosophical foundations of digital twinning, Preprint]) as well as the (interpretable) units that constitute the whole.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Mitochondrial trifunctional protein deficiency is a long-chain fatty acid disorder that may include manifestations of severe cardiomyopathy and arrhythmias. The pathophysiology for the severe presentation is unclear but is an indicator for worse outcomes. Triheptanoin, a synthetic medium chain triglyceride, has been reported to reverse cardiomyopathy in some individuals, but there is limited literature in severe cases. We describe a neonatal onset of severe disease whose clinical course was not improved despite mechanical support and triheptanoin.
Several metrics exist for matching the size of donor to recipient in paediatric cardiac transplantation. Different centres employ different metrics for size-matching to determine the viability of donor hearts. Inconsistent evidence exists, with limited consensus as to the metric for size-matching that is most predictive of outcomes after cardiac transplantation. Furthermore, any metric must function within the tight timeline available for the assessment of the suitability of the donor. At the time of the writing of this paper, the most commonly used metric for size-matching in paediatric cardiac transplantation is the donor-to-recipient body weight ratio. In this article, we review published literature evaluating commonly used metrics for size-matching in paediatric cardiac transplantation, including weight, height, body surface area, and imaging parameters.