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.
Adolescent and parental perceptions of the Fontan Udenafil Exercise Longitudinal Assessment Randomised Controlled Trial (FUEL) and its open-label extension were examined, to identify factors affecting future research participation.
Methods:
A validated survey was administered at two time points to adolescents (12–19 years) and their parents to assess likes/dislikes of study participation, research team, study burden and benefits. A 5-point Likert scale (strongly disagree [−2] to strongly agree [ + 2]) was used, and scores were averaged. Regression models explored potential predictors. Open-ended questions queried the most/least appealing aspects of participation and considerations for future research.
Results:
Among 250 FUEL participants at 14 centres, 179 adolescent and 183 parent surveys were completed at T1 (6 months after randomisation). Perceptions of research participation were generally positive: 1.35 ± 0.45 for adolescents; 1.56 ± 0.38 (p < 0.001) for parents. There were no significant differences between females vs. males. Themes from open-ended responses included liking to help others and themselves, liking the study team, and disliking study burden. Adolescents liked the compensation and disliked study-related testing. At T2 (end of open-label extension study), 121 adolescents and 114 parents responded. Perception scores remained high at 1.39 ± 0.51 for adolescents and 1.58 ± 0.37 for parents (p = 0.001). There were no significant gender differences in perceptions between adolescents, but mothers had slightly better perceptions than fathers (p = 0.004).
Conclusions:
Perceptions of research were positive and slightly better for parents. Study teams and compensation were key contributors to positive perceptions. Study burden and testing were viewed less favourably. Future studies should consider families’ preferences and potential barriers to participation.
An important component of post-release monitoring of biological control of invasive plants is the tracking of species interactions. During post-release monitoring following the initial releases of the weevil Ceutorhynchus scrobicollis Nerenscheimer and Wagner (Coleoptera: Curculionidae) on garlic mustard, Alliaria petiolata (Marschall von Bieberstein) Cavara and Grande (Brassicaceae), in Ontario, Canada, we identified the presence of larvae of the tumbling flower beetle, Mordellina ancilla Leconte (Coleoptera: Mordellidae), in garlic mustard stems. This study documents the life history of M. ancilla on garlic mustard to assess for potential interactions between M. ancilla and C. scrobicollis as a biological control agent. Garlic mustard stems were sampled at eight sites across southern Ontario and throughout the course of one year to record the prevalence of this association and to observe its life cycle on the plant. We found M. ancilla to be a widespread stem-borer of late second–year and dead garlic mustard plants across sampling locations. This is the first host record for M. ancilla on garlic mustard. The observed life cycle of M. ancilla indicates that it is unlikely to negatively impact the growth and reproduction of garlic mustard and that it is unlikely to affect the use of C. scrobicollis as a biological control agent.
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.
To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.
Design:
Retrospective cohort study.
Setting:
Community health system.
Patients:
Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10–14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.
Methods:
Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.
Results:
The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07–0.56, p < 0.002).
Conclusions:
Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.
Data compilations expand the scope of research; however, data citation practice lags behind advances in data use. It remains uncommon for data users to credit data producers in professionally meaningful ways. In paleontology, databases like the Paleobiology Database (PBDB) enable assessment of patterns and processes spanning millions of years, up to global scale. The status quo for data citation creates an imbalance wherein publications drawing data from the PBDB receive significantly more citations (median: 4.3 ± 3.5 citations/year) than the publications producing the data (1.4 ± 1.3 citations/year). By accounting for data reuse where citations were neglected, the projected citation rate for data-provisioning publications approached parity (4.2 ± 2.2 citations/year) and the impact factor of paleontological journals (n = 55) increased by an average of 13.4% (maximum increase = 57.8%) in 2019. Without rebalancing the distribution of scientific credit, emerging “big data” research in paleontology—and science in general—is at risk of undercutting itself through a systematic devaluation of the work that is foundational to the discipline.
Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.
This study compared the per capita annual global incidence rate of disasters caused by natural hazards with the annual world real gross domestic product, GDP (per global capita), as reported during 1961 through 2020.
Methods:
Sixty (60) values for the world real GDP per global capita (in constant 2015 $USD) were compared to corresponding annual values for global incidence rates for five natural disaster subgroups and then for a total of twelve individual disaster types that comprise the subgroups; each expressed as an annual global incidence rate (in terms of annual incidence per 100,000 persons). Calculations of multiple linear regression, ANOVA, and Pearson’s correlation coefficient were performed for comparing population-adjusted values for GDP to corresponding values.
Results:
Four out of five hydrological and meteorological disasters were found to have a positive correlation with GDP. Results of the analysis revealed a relatively high degree of correlation between world GDP and the annual incidence of flood and storm disasters (P = 6.21 × 10−10 and P = 4.23 × 10−4, respectively). The annual incidence of heat waves and cold weather disasters also appeared to correlate with GDP (P = .002 and P = .019, respectively). In comparison, wet landslides indicated no such correlation (P = .862). No significant associations were found among the seven other individual biological, climatological, and geophysical disasters and GDP.
Conclusion:
The global incidence of four extreme weather (hydrometeorological) disasters appear to be positively associated with world real GDP during 1961-2020. These findings contradict previous postulates that the risk of disaster incidence is inversely associated with the capacity of the population.
Fluting is a technological and morphological hallmark of some of the most iconic North American Paleoindian stone points. Through decades of detailed artifact analyses and replication experiments, archaeologists have spent considerable effort reconstructing how flute removals were achieved, and they have explored possible explanations of why fluting was such an important aspect of early point technologies. However, the end of fluting has been less thoroughly researched. In southern North America, fluting is recognized as a diagnostic characteristic of Clovis points dating to approximately 13,000 cal yr BP, the earliest widespread use of fluting. One thousand years later, fluting occurs more variably in Dalton and is no longer useful as a diagnostic indicator. How did fluting change, and why did point makers eventually abandon fluting? In this article, we use traditional 2D measurements, geometric morphometric (GM) analysis of 3D models, and 2D GM of flute cross sections to compare Clovis and Dalton point flute and basal morphologies. The significant differences observed show that fluting in Clovis was highly standardized, suggesting that fluting may have functioned to improve projectile durability. Because Dalton points were used increasingly as knives and other types of tools, maximizing projectile functionality became less important. We propose that fluting in Dalton is a vestigial technological trait retained beyond its original functional usefulness.
Field studies were conducted to determine the effects of synthetic auxin herbicides at simulated exposure rates applied to ‘Covington’ sweetpotato propagation beds on the quality of nonrooted stem cuttings (slips). Treatments included diglycolamine salt of dicamba, 2,4-D choline plus nonionic surfactant (NIS), and 2,4-D choline plus glyphosate at 1/10, 1/33, or 1/66 of a 1X application rate (560 g ae ha−1 dicamba, 1,065 g ae ha−1 2,4-D choline, 1,130 g ae ha−1 glyphosate) applied at 2 or 4 wk after first slip harvest (WASH). Injury to sweetpotato 2 wk after treatment was greatest when herbicides were applied 2 WASH (21%) compared to 4 WASH (16%). More slip injury was caused by 2,4-D choline than by dicamba, and the addition of glyphosate did not increase injury over 2,4-D choline alone. Two weeks after the second application, sweetpotato slips were cut 2 cm above the soil surface and transplanted into production fields. In 2019, sweetpotato ground coverage 8 wk after transplanting was reduced 37% and 26% by the 1/10X rates of dicamba and 2,4-D choline plus NIS, respectively. Though dicamba caused less injury to propagation beds than 2,4-D choline with or without glyphosate, after transplanting, slips treated with 1/10X dicamba did not recover as quickly as those treated with 2,4-D choline. In 2020, sweetpotato ground coverage was 90% or greater for all treatments. Dicamba applied 2 WASH decreased marketable sweetpotato storage root yield by 59% compared to the nontreated check, whereas treatments including 2,4-D choline reduced marketable yield 22% to 29%. All herbicides applied at 4 WASH reduced marketable yield 31% to 36%. The addition of glyphosate to 2,4-D choline did not increase sweetpotato yield. Results indicate that caution should be taken when deciding whether to transplant sweetpotato slips that are suspected to have been exposed to dicamba or 2,4-D choline.
Records of abnormal fossil arthropods present important insight into how extinct forms responded to traumatic damage and developmental complications. Trilobites, bearing biomineralized dorsal exoskeletons, have arguably the most well-documented record of abnormalities spanning the Cambrian through the end-Permian. As such, new records of malformed, often injured, trilobites are occasionally identified. To further expand the documentation of abnormal specimens, we describe malformed specimens of Lyriaspis sigillum Whitehouse, 1939, Zacanthoides sp. indet., Asaphiscus wheeleri Meek, 1873, Elrathia kingii (Meek, 1870), and Ogygiocarella debuchii (Brongniart, 1822) from lower Paleozoic deposits. In considering these forms, we propose that they illustrate examples of injuries, and that the majority of these injuries reflect failed predation. We also considered the origin of injuries impacting singular segments, suggesting that these could reflect predation, self-induced damage, or intraspecific interactions during soft-shelled stages. Continued examination of lower Paleozoic trilobite injuries will further the understanding of how trilobites functioned as prey and elucidate how disparate trilobite groups recovered from failed attacks.
Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18–30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.
Transforming towards global sustainability requires a dramatic acceleration of social change. Hence, there is growing interest in finding ‘positive tipping points’ at which small interventions can trigger self-reinforcing feedbacks that accelerate systemic change. Examples have recently been seen in power generation and personal transport, but how can we identify positive tipping points that have yet to occur? We synthesise theory and examples to provide initial guidelines for creating enabling conditions, sensing when a system can be positively tipped, who can trigger it, and how they can trigger it. All of us can play a part in triggering positive tipping points.
Technical summary
Recent work on positive tipping points towards sustainability has focused on social-technological systems and the agency of policymakers to tip change, whilst earlier work identified social-ecological positive feedbacks triggered by diverse actors. We bring these together to consider positive tipping points across social-technological-ecological systems and the potential for multiple actors and interventions to trigger them. Established theory and examples provide several generic mechanisms for triggering tipping points. From these we identify specific enabling conditions, reinforcing feedbacks, actors and interventions that can contribute to triggering positive tipping points in the adoption of sustainable behaviours and technologies. Actions that can create enabling conditions for positive tipping include targeting smaller populations, altering social network structure, providing relevant information, reducing price, improving performance, desirability and accessibility, and coordinating complementary technologies. Actions that can trigger positive tipping include social, technological and ecological innovations, policy interventions, public investment, private investment, broadcasting public information, and behavioural nudges. Positive tipping points can help counter widespread feelings of disempowerment in the face of global challenges and help unlock ‘paralysis by complexity’. A key research agenda is to consider how different agents and interventions can most effectively work together to create system-wide positive tipping points whilst ensuring a just transformation.
Social media summary
We identify key actors and actions that can enable and trigger positive tipping points towards global sustainability.
We examined the associations between the developmental timing of interpersonal trauma exposure (IPT) and three indicators of involvement in and quality of romantic relationships in emerging adulthood: relationship status, relationship satisfaction, and partner alcohol use. We further examined whether these associations varied in a sex-specific manner. In a sample of emerging adult college students (N = 12,358; 61.5% female) assessed longitudinally across the college years, we found precollege IPT increased the likelihood of being in a relationship, while college-onset IPT decreased the likelihood. Precollege and college-onset IPT predicted lower relationship satisfaction, and college-onset IPT predicted higher partner alcohol use. There was no evidence that associations between IPT and relationship characteristics varied in a sex-specific manner. Findings indicate that IPT exposure, and the developmental timing of IPT, may affect college students’ relationship status. Findings also suggest that IPT affects their ability to form satisfying relationships with prosocial partners.
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.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Methods:
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
Results:
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Conclusions:
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
We performed a prospective study of 501 patients, regardless of symptoms, admitted to the hospital, to estimate the predictive value of a negative nasopharyngeal swab for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). At a positivity rate of 10.2%, the estimated negative predictive value (NPV) was 97.2% and the NPV rose as prevalence decreased during the study.
Social cognitive deficits can have many negative consequences, spanning social withdrawal to psychopathology. Prior work has shown that child maltreatment may associate with poorer social cognitive skills in later life. However, no studies have examined this association from early childhood into adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4,438), we examined the association between maltreatment (caregiver physical or emotional abuse; sexual or physical abuse), assessed repeatedly (every 1–3 years) from birth to age 9, and social cognitive skills at ages 7.5, 10.5, and 14 years. We evaluated the role of both the developmental timing (defined by age at exposure) and accumulation of maltreatment (defined as the number of occasions exposed) using a least angle regression variable selection procedure, followed by structural equation modeling. Among females, accumulation of maltreatment explained the most variation in social cognitive skills. For males, no significant associations were found. These findings underscore the importance of early intervention to minimize the accumulation of maltreatment and showcase the importance of prospective studies to understand the development of social cognition over time.
Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.