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Precise stratification of patients into homogeneous disease subgroups could address the heterogeneity of phenotypes and enhance understanding of the pathophysiology underlying specific subtypes. Existing literature on subtyping patients with major depressive disorder (MDD) mainly utilized clinical features only. Genomic and imaging data may improve subtyping, but advanced methods are required due to the high dimensionality of features.
Methods
We propose a novel disease subtyping framework for MDD by integrating brain structural features, genotype-predicted expression levels in brain tissues, and clinical features. Using a multi-view biclustering approach, we classify patients into clinically and biologically homogeneous subgroups. Additionally, we propose approaches to identify causally relevant genes for clustering.
Results
We verified the reliability of the subtyping model by internal and external validation. High prediction strengths (PS) (average PS: 0.896, minimum: 0.854), a measure of generalizability of the derived clusters in independent datasets, support the validity of our approach. External validation using patient outcome variables (treatment response and hospitalization risks) confirmed the clinical relevance of the identified subgroups. Furthermore, subtype-defining genes overlapped with known susceptibility genes for MDD and were involved in relevant biological pathways. In addition, drug repositioning analysis based on these genes prioritized promising candidates for subtype-specific treatments.
Conclusions
Our approach successfully stratified MDD patients into subgroups with distinct clinical prognoses. The identification of biologically and clinically meaningful subtypes may enable more personalized treatment strategies. This study also provides a framework for disease subtyping that can be extended to other complex disorders.
The EU's non-financial reporting (NFR) regulations have significant impacts on Global South stakeholders, firms that must report, actors lower in the value chain, and organisations seeking investment from NFR-compliant firms or institutions. This paper sets forth six proposals to improve the global equity and sustainability implications of the EU's NFR from a Global South perspective. The proposals involve (1) developing regulation cooperatively with the Global South; (2) streamlining reporting to enable the regulations to have real effects and limit incorrect accounting; (3) digitalising reporting through accessible technologies for greater accountability and lower administrative burdens; (4) mandating scope 3 emissions accounting and incentivising related investment; (5) anchoring financial institutions' role in ethical investment and bridging Northern and Southern actors; and (6) strengthening citizen data and sustainability literacy to close the circle of incentives, implementation, and impact.
This work investigates the spatio-temporal evolution of coherent structures in the wake of a generic high-speed train, based on a three-dimensional database from large eddy simulation. Spectral proper orthogonal decomposition (SPOD) is used to extract energy spectra and energy ranked empirical modes for both symmetric and antisymmetric components of the fluctuating flow field. The spectrum of the symmetric component shows overall higher energy and more pronounced low-rank behaviour compared with the antisymmetric one. The most dominant symmetric mode features periodic vortex shedding in the near wake, and wave-like structures with constant streamwise wavenumber in the far wake. The mode bispectrum further reveals the dominant role of self-interaction of the symmetric component, leading to first harmonic and subharmonic triads of the fundamental frequency, with remarkable deformation of the mean field. Then, the stability of the three-dimensional wake flow is analysed based on two-dimensional local linear stability analysis combined with a non-parallelism approximation approach. Temporal stability analysis is first performed for both the near-wake and the far-wake regions, showing a more unstable condition in the near-wake region. The absolute frequency of the near-wake eigenmode is determined based on spatio-temporal analysis, then tracked along the streamwise direction to find out the global mode growth rate and frequency, which indicate a marginally stable global mode oscillating at a frequency very close to the most dominant SPOD mode. The global mode wavemaker is then located, and the structural sensitivity is calculated based on the direct and adjoint modes derived from a local spatial analysis, with the maximum value localized within the recirculation region close to the train tail. Finally, the global mode shape is computed by tracking the most spatially unstable eigenmode in the far wake, and the alignment with the SPOD mode is computed as a function of streamwise location. By combining data-driven and theoretical approaches, the mechanisms of coherent structures in complex wake flows are well identified and isolated.
A conceptual framework, called Innovation of Health Technology Assessment Methods (IHTAM), has been developed to facilitate the understanding of how to innovate methods of health technology assessment (HTA). However, the framework applicability has not been evaluated in practice. Hence, we aimed to explore framework applicability in three cases of method innovation that are part of the HTx project and to develop a roadmap to improve framework applicability.
Methods
The IHTAM framework was applied to three cases of innovating HTA methods. We collected feedback from case study leaders and consortium members after a training session, an approximately 1-year follow-up of periodic case study meetings, and a general assembly meeting where innovation progresses of the three cases were reported through surveys and interviews. Feedback was then summarized using an open-coding technique.
Results
According to feedback, the framework provided a structured way of deliberation and helped to improve collaboration among HTA stakeholders. However, framework applicability could be improved if it was complemented by a roadmap with a loop structure to provide tailored guidance for different cases, and with items to elaborate actions to be taken by stakeholders. Accordingly, a 48-item roadmap was developed.
Conclusions
The IHTAM framework was generally applicable to the three case studies. A roadmap, with loop structure and actionable items, could complement the framework, and may provide HTA stakeholders with tailored guidance on developing new methods. To further examine the framework applicability, we recommend stakeholders to apply the IHTAM framework and its roadmap in future practice.
Identifying the absence of situation awareness (SA) in air traffic controllers is critical since it directly affects their hazard perception. This study aims to introduce and validate a multimodal methodology employing electroencephalogram (EEG) and eye-tracking to investigate SA variation within specific air traffic control contexts. Data from 28 participants executing the experiment involving three different SA-probe tests illustrated the conceptual relationship between EEG and eye-tracking indicators and SA variations, using behavioural data as a proxy. The results indicated that both EEG and eye-tracking metrics correlated positively with the SA levels required, that is, the frequency spectrum in the β (13–30 Hz) and γ (30–50 Hz) bands, alongside the fixation/saccade-based indicators and pupil dilation increased in response to higher SA levels. This research has substantial implications for investigating SA using a human-centric approach via psychophysiological indicators, revealing the intrinsic interactions between the human capability envelope and SA, contributing to the development of a real-time monitoring system of SA variations for air transportation safety research.
Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.
Methods
After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.
Results
The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.
Conclusions
These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.
Daqingshan is located in the northwestern North China Craton where late Neoarchaean supracrustal rocks occur widely, but where magmatic zircon ages have rarely been reported for plutonic rocks. In this study, we report SIMS U–Pb zircon ages and Hf isotope, whole-rock element and Nd isotope compositions for 12 magmatic samples, including TTG, quartz monzonitic and monzogranitic gneisses, and meta-gabbroic and dioritic rocks. They have magmatic zircon ages of 2530–2469 Ma; some samples have ages of <2.48 Ga likely influenced by late Palaeoproterozoic tectonothermal events, making their ages less reliable. TTG gneisses have low Sr/Y and La/Yb ratios, with whole-rock ϵNd(t) and in situ magmatic zircon ϵHf(t) values of +1.2 to +2.4 and −1.1 to +6.2, respectively. Quartz monzonite and monzogranite gneisses and gabbroic to dioritic rocks have similar Nd–Hf isotope compositions to the TTG gneisses. The absence of zircon >2.6 Ga in the early Precambrian rocks suggests that the Sanggan Group may have formed in an oceanic environment, whereas the TTG rocks formed as a result of partial melting of the basaltic rocks of the Sanggan Group under relatively low-pressure conditions. Combined with previous studies, the main conclusions are that in the Daqingshan area, late Neoarchaean magmatism was widespread, the late Mesoarchaean – early Neoarchaean was an important period of juvenile continental crustal growth, and the late Neoarchaean supracrustal and plutonic rocks most likely formed in an arc environment. These are common signatures for Neoarchaean crustal evolution throughout much of the North China Craton, and also globally.
The Maser Monitoring Organisation is a collection of researchers exploring the use of time-variable maser emission in the investigation of astrophysical phenomena. The forward directed aspects of research primarily involve using maser emission as a tool to investigate star formation. Simultaneously, these activities have deepened knowledge of maser emission itself in addition to uncovering previously unknown maser transitions. Thus a feedback loop is created where both the knowledge of astrophysical phenomena and the utilised tools of investigation themselves are iteratively sharpened. The project goals are open-ended and constantly evolving, however, the reliance on radio observatory maser monitoring campaigns persists as the fundamental enabler of research activities within the group.
Recently, remarkable progress has been made in understanding the formation of high mass stars. Observations provided direct evidence that massive young stellar objects (MYSOs), analogously to low-mass ones, form via disk-mediated accretion accompanied by episodic accretion bursts, possibly caused by disk fragmentation. In the case of MYSOs, the mechanism theoretically provides a means to overcome radiation pressure, but in practice it is poorly studied - only three accretion bursts in MYSOs have been caught in action to date. A significant contribution to the development of the theory has been made with the study of masers, which have proven to be a powerful tool for locating “bursting” MYSOs. This overview focuses on the exceptional role that masers play in the search and study of accretion bursts in massive protostars.
We obtained 24 air samples in 8 general wards temporarily converted into negative-pressure wards admitting coronavirus disease 2019 (COVID-19) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant BA.2.2 in Hong Kong. SARS-CoV-2 RNA was detected in 19 (79.2%) of 24 samples despite enhanced indoor air dilution. It is difficult to prevent airborne transmission of SARS-CoV-2 in hospitals.
Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown.
Methods:
We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed.
Results:
Of 20 singly isolated patients with median age of 30 months (range, 3 months–15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020).
Conclusion:
Air dispersal of common respiratory viruses may have infection prevention and public health implications.
Perfectionism, low self-esteem and external locus of control are psychological constructs linked to insomnia, anxiety and depression. Examining how these constructs impact mental health and serve as risk factors for the development of clinically significant symptoms may help direct psychological support resources and preventative measures for university students.
Aims
To longitudinally examine associations between the aforementioned psychological constructs and symptoms of insomnia, anxiety and depression in a large representative sample of first-year university students.
Method
Electronic surveys including validated measures of the predictors and outcomes were emailed to all first-year undergraduate students at entry to a major Canadian university, and followed up on at conclusion of the academic year.
Results
Compared with healthy sleepers, students screening positive for insomnia had lower self-esteem, higher self-evaluative perfectionism and increased external locus of control (all P < 0.001). Self-evaluative perfectionism (standardised β = 0.13, P < 0.01), self-esteem (β = −0.30, P < 0.001) and external locus of control (β = 0.07, P = 0.02) measured at entry were significantly associated with insomnia symptoms at follow-up. Insomnia symptoms at entry were strong predictors of symptoms of depression (β = 0.15, P < 0.001) and anxiety (β = 0.16, P < 0.001) at follow-up, even after controlling for baseline symptoms of those disorders.
Conclusions
Perfectionism, low self-esteem and external locus of control may predispose the development of insomnia symptoms in university students. In turn, insomnia symptoms appear to be robust predictors for depressive and anxiety symptoms. Sleep may be an important prevention target in university students.
Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention.
Methods
360 psychosis patients aged 26–55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years.
Results
Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001–0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004–0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year.
Conclusions
Specialized EI treatment for psychosis patients aged 26–55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.
Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).
Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Throughout the Ediacaran Period, variable water-column redox conditions persisted along productive ocean margins due to a complex interplay between nutrient supply and oceanographic restriction. These changing conditions are considered to have influenced early faunal evolution, with marine anoxia potentially inhibiting the development of the ecological niches necessary for aerobic life forms. To understand this link between oxygenation and evolution, the combined geochemical and palaeontological study of marine sediments is preferable. Located in the Yangtze Gorges region of southern China, lagoonal black shales at Miaohe preserve alga and putative metazoans, including Eoandromeda, a candidate total-group ctenophore, thereby providing one example of where integrated study is possible. We present a multi-proxy investigation into water-column redox variability during deposition of these shales (c. 560–551 Ma). For this interval, reactive iron partitioning indicates persistent water-column anoxia, while trace metal enrichments and other geochemical data suggest temporal fluctuations between ferruginous, euxinic and rare suboxic conditions. Although trace metal and total organic carbon values imply extensive basin restriction, sustained trace metal enrichment and δ15Nsed data indicate periodic access to open-ocean inventories across a shallow-marine sill. Lastly, δ13Corg values of between −35‰ and −40‰ allow at least partial correlation of the shales at Miaohe with Member IV of the Doushantuo Formation. This study provides evidence for fluctuating redox conditions in the lagoonal area of the Yangtze platform during late Ediacaran time. If these low-oxygen environments were regionally characteristic, then the restriction of aerobic fauna to isolated environments can be inferred.
We construct a double common factor model for projecting the mortality of a population using as a reference the minimum death rate at each age among a large number of countries. In particular, the female and male minimum death rates, described as best-performance or best-practice rates, are first modelled by a common factor model structure with both common and sex-specific parameters. The differences between the death rates of the population under study and the best-performance rates are then modelled by another common factor model structure. An important result of using our proposed model is that the projected death rates of the population being considered are coherent with the projected best-performance rates in the long term, the latter of which serves as a very useful reference for the projection based on the collective experience of multiple countries. Our out-of-sample analysis shows that the new model has potential to outperform some conventional approaches in mortality projection.
To compare sensitivity of specimens for COVID-19 diagnosis, we tested 151 nasopharyngeal/midturbinate swab pairs from 117 COVID-19 inpatients using reverse-transcriptase polymerase chain reaction (RT-PCR). Sensitivity was 94% for nasopharyngeal and 75% for midturbinate swabs (P = .0001). In 88 nasopharyngeal/midturbinate pairs with matched saliva, sensitivity was 86% for nasopharyngeal swabs and 88% for combined midturbinate swabs/saliva.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
We present a long-term seasonal tree ring cellulose oxygen isotope (δ18Oc) time series created by analyzing four segments (S1, S2, S3, and S4) per year during the period of 1951–2009 from southeastern Tibetan Plateau. This intraseasonal δ18Oc reveals the onset and mature phase of the summer monsoon precipitation in this region. Analysis indicates that the δ18Oc of S1 has the strongest correlation with precipitation during the regional monsoon onset (29–33 pentads, May 21–June 10, r = −0.69), and the δ18Oc values for S2, S3, and S4 correlate strongly with June, July, and August precipitation, respectively. Combined δ18Oc of S2, S3, and S4 shows the most robust correlation (r = −0.82) with the mature-phase monsoon precipitation (June-July-August, JJA), passing rigorous statistical tests for calibration and verification in dendroclimatology. These results demonstrate the feasibility in using long-term intraseasonal δ18Oc to reconstruct the Asian summer monsoon's intraseasonal variations.