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Considering that causal mechanisms unfold over time, it is important to investigate the mechanisms over time, taking into account the time-varying features of treatments and mediators. However, identification of the average causal mediation effect in the presence of time-varying treatments and mediators is often complicated by time-varying confounding. This article aims to provide a novel approach to uncovering causal mechanisms in time-varying treatments and mediators in the presence of time-varying confounding. We provide different strategies for identification and sensitivity analysis under homogeneous and heterogeneous effects. Homogeneous effects are those in which each individual experiences the same effect, and heterogeneous effects are those in which the effects vary over individuals. Most importantly, we provide an alternative definition of average causal mediation effects that evaluates a partial mediation effect; the effect that is mediated by paths other than through an intermediate confounding variable. We argue that this alternative definition allows us to better assess at least a part of the mediated effect and provides meaningful and unique interpretations. A case study using ECLS-K data that evaluates kindergarten retention policy is offered to illustrate our proposed approach.
Problem Management Plus (PM+) has been effective in reducing mental health problems among refugees at three-month follow-up, but there is a lack of research on its long-term effectiveness. This study examined the effectiveness of PM+ in reducing symptoms of common mental disorders at 12-month follow-up among Syrian refugees in the Netherlands.
Methods
This single-blind, parallel, controlled trial randomised 206 adult Syrians who screened positive for psychological distress and impaired functioning to either PM+ in addition to care as usual (PM+/CAU) or CAU alone. Assessments were at baseline, 1 week and 3 months after the intervention and 12 months after baseline. Outcomes were psychological distress (Hopkins Symptom Checklist [HSCL-25]), depression (HSCL-25 subscale), anxiety (HSCL-25 subscale), posttraumatic stress disorder symptoms (PCL-5), functional impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS).
Results
In March 2019–December 2022, 103 participants were assigned to PM+/CAU and 103 to CAU of which 169 (82.0%) were retained at 12 months. Intention-to-treat analyses showed greater reductions in psychological distress at 12 months for PM+/CAU compared to CAU (adjusted mean difference −0.17, 95% CI −0.310 to −0.027; p = 0.01, Cohen’s d = 0.28). Relative to CAU, PM+/CAU participants also showed significant reductions on anxiety (−0.19, 95% CI −0.344 to −0.047; p = 0.01, d = 0.31) but not on any of the other outcomes.
Conclusions
PM+ is effective in reducing psychological distress and symptoms of anxiety over a period up to 1 year. Additional support such as booster sessions or additional (trauma-focused) modules may be required to prolong and consolidate benefits gained through PM+ on other mental health and psychosocial outcomes.
Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.
Methods:
We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.
Results:
We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.
Conclusion:
PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.
Scholars contend that the reason for stasis in human rights measures is a biased measurement process, rather than stagnating human rights practices. We argue that bias may be introduced as part of the compilation of the human rights reports that serve as the foundation of human rights measures. An additional source of potential bias may be human coders, who translate human rights reports into human rights scores. We first test for biases via a machine-learning approach using natural language processing and find substantial evidence of bias in human rights scores. We then present findings of an experiment on the coders of human rights reports to assess whether potential changes in the coding procedures or interpretation of coding rules affect scores over time. We find no evidence of coder bias and conclude that human rights measures have changed over time and that bias is introduced as part of monitoring and reporting.
While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.
Methods
The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner.
Results
We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating.
Conclusions
The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of ‘neural efficiency’ (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.
Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment.
Methods
We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association.
Results
Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics.
Conclusions
Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences.
Among the knots that are the connected sum of two torus knots with cobordism distance 1, we characterise those that have 4-dimensional clasp number at least 2, and we show that their n-fold connected self-sum has 4-dimensional clasp number at least 2n. Our proof works in the topological category. To contrast this, we build a family of topologically slice knots for which the n-fold connected self-sum has 4-ball genus n and 4-dimensional clasp number at least 2n.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
Background: Estimating the burden of intestinal colonization with antibiotic-resistant gram-negative bacteria (AR-GNB) is critical to understanding their global epidemiology and spread. We aimed to determine the prevalence of, and risk factors for, intestinal colonization due to AR-GNB in population-based hospital and community settings in Chile. Methods: Between December 2018 and May 2019, we enrolled randomly selected hospitalized adults in 4 tertiary-care public hospitals (Antofagasta, Santiago, Curico and Puerto Montt), and adults residing in a community-based cohort in the rural town of Molina. Following informed consent, we collected rectal swabs and epidemiological information through a standardized questionnaire. Swabs were plated onto MacConkey agar with 2 µg/mL ciprofloxacin or ceftazidime. All recovered morphotypes were identified, and antibiotic susceptibility testing was performed via disk diffusion. The primary outcome was the prevalence of colonization with fluoroquinolone (FQ)- or third-generation cephalosporin (3GC)–resistant GNB. The secondary outcome was the prevalence of colonization with multidrug-resistant (MDR) GNB, defined as GNB resistant to ≥3 antibiotic classes. Categories were not mutually exclusive. Bivariate and multivariate analyses were performed to describe risk factors for colonization with these categories. Results: In total, 775 hospitalized adults and 357 community participants were enrolled, with a median age of 60 years (IQR, 42–72) and 55 years (IQR, 48–62) years, respectively. Among hospitalized participants, the prevalence of colonization with FQ- or 3GC-resistant GNB was 47% (95% CI, 43%–50%) and 41% (95% CI, 38%–45%), respectively, whereas the prevalence of MDR-GNB colonization was 27% (95% CI, 24%–31%). In the community setting, the prevalence of colonization with either FQ-, 3GC-resistant GNB, or MDR-GNB was 40% (95% CI, 34%–45%), 29% (95% CI, 24%– 34%), and 5% (95% CI, 3%–8%), respectively. Independent risk factors for hospital MDR-GNB colonization included the hospital of admission, unit of hospitalization (intensive care units carried the highest risk), in-hospital antimicrobial exposure, comorbidities (Charlson index), and length of stay. In the community setting, recent antibiotic exposure (<3 months) predicted colonization with either FQ- or 3GC-resistant GNB, and alcohol consumption was inversely associated with MDR GNB colonization. Conclusions: A high burden of colonization with AR-GNB was observed in this sample of hospitalized and community-dwelling adults in Chile. The high burden of colonization with GNB resistant to commonly used antibiotics such as FQ and 3GC found in community dwellers, suggests that the community may be a relevant source of antibiotic resistance. Efforts to understand relatedness between resistant strains circulating in the community and the hospital are needed.
Calcium–magnesium–alumino-silicate (CMAS) particulates enter the aero-engine in a sandy environment, melt and infiltrate into 7 wt% yttria-stabilized zirconia (7YSZ) thermal barrier coatings (TBCs), reducing their lifetime. This leads to chemical degradation in 7YSZ accompanied by tetragonal to monoclinic phase transformation upon cooling. In this work, electron-beam physical vapor deposition coatings were infiltrated with a synthetic CMAS. Synchrotron X-ray diffraction measurements show that CMAS infiltration at 1250 °C has about 43% higher monoclinic phase volume fraction (PVF) at the coating surface compared to 1225 °C and remains consistently higher throughout the coating depth. Additionally, the increase in annealing time from 1 to 10 h results in a 31% higher monoclinic phase at the surface. Scanning electron microscopy revealed the presence of globular monoclinic phases corresponding spatially with the above findings. These results resolve the impact of time and temperature on CMAS infiltration kinetics which is important for mitigation.
A 1108.6 m long core was recovered at Site U1457 located on the Indus Fan in the Laxmi Basin of the eastern Arabian Sea during IODP Expedition 355. Shipboard examinations defined five lithologic units (I to V) of the lower Paleocene to Holocene sedimentary sequence. In this study, δ13C values of sedimentary organic matter (SOM) confirm the differentiation of the lithologic units and further divide units III and IV into two subunits (1 and 2). Based on the underlying assumption that the SOM is decided primarily by a mixture of marine and terrestrial origins, δ13CSOM values at Site U1457 provide information on the terrestrial catchment conditions since late Miocene time. Low δ13CSOM values from late Miocene to late Pleistocene times are similar (c. −22.0 ‰) for the most part, reflecting a consistent contribution of terrestrial organic matter from the catchment areas characterized by dominant C3 land plants. Significantly lower δ13CSOM values (c. −24.0 ‰) in Unit III-2 (∼8 to ∼7 Ma) might be due to a greater input of C3 terrestrial organic matter. The increase in δ13CSOM values at ∼7 Ma and the appearance of high δ13CSOM values (c. −18.0 ‰) within Unit III-1 (∼7 to ∼2 Ma) indicate that C4 biomass overwhelmed the terrestrial catchment environment as a result of enhanced terrestrial aridity in the Himalayan foreland. The three-end-member simple mixing model, estimating the relative contributions of SOM from terrestrial C3 and C4 plants and marine phytoplankton, supports our interpretation of the distribution of C3 and C4 land plants in the terrestrial catchment environment.
Cantors made unparalleled contributions to the way time was understood and history was remembered in the medieval Latin West. The men and women who held this office in cathedrals and monasteries wereresponsible for calculating the date of Easter and the feasts dependent on it, for formulating liturgical celebrations season by season, managing the library and preparing manuscripts and other sources necessary to sustain the liturgical framework of time, and promoting the cults of saints. Crucially, their duties also often included committing the past to writing, from simple annals and chronicles to more fulsome histories, necrologies, and cartularies, thereby ensuring that towns, churches, families, and individuals could be commemorated for generations to come. The contributions hereseek to address the fundamental question of how the range of cantors' activities can help us to understand the many different ways in which the past was written and, in the liturgy, celebrated acrossthe middle ages. Cantors, as this volume makes clear, shaped the communal experience of the past in the Middle Ages; the essays are studies of constructions, both of the building blocks of time and ofthe people who made and performed them, in acts of ritual remembrance and in written records.
Contributors: Cara Aspesi, Alison I. Beach, Katie Ann-Marie Bugyis, Margot E. Fassler, David Ganz, James Grier, Paul Antony Hayward, A.B. Kraebel, Lori Kruckenberg, Rosamond McKitterick, Henry Parkes, Susan Rankin, C.C. Rozier, Sigbjoryn Olsen Sonnesyn, Teresa Webber, Lauren Whitnah,
Interferometric synthetic aperture radar (InSAR) observations of ice-shelf flow contain ocean-tide and atmospheric-pressure signals. A model-based correction can be applied, but this method is limited by its dependency upon model accuracy, which in remote regions can be uncertain. Here we describe a method to determine two-dimensional ice-shelf flow vectors independently of model predictions of tide and atmospheric pressure, by stacking conventional and multiple aperture InSAR (MAI) observations of the Dotson Ice Shelf, West Antarctica. In this way we synthesize a longer observation period, which enhances long-period (flow) displacement signals, relative to rapidly varying (tide and atmospheric pressure) signals and noise. We estimate the error associated with each component of the velocity field to be ~22 ma-1, which could be further reduced if more images were available to stack. With the upcoming launch of several satellite missions, offering the prospect of regular short-repeat SAR acquisitions, this study demonstrates that stacking can improve estimates of ice-shelf flow velocity.
‘History’, as it was understood by medieval Christians, was a broad concept with many meanings. It could be defined as a written record, compiled through processes inherited from classical Greek and Roman authors. But even when it proclaimed itself to be ‘factual’, the work of those who shaped the past in the Latin Middle Ages was different from that of their pagan ancestors. Although they often made claims about veracity, even when dealing with the miraculous, they did not ‘absolutize’ history (as de Lubac put it). Although they had a sense of universal history, time instead related to and unfolded within a framework conditioned by the Incarnation of the Word, and by the moral sense that this history-transforming event could impart to listeners and readers. The biblical orientation of history gave time a clear beginning and also predicted an apocalyptic end. But even as time moved relentlessly forward in this cosmic sense, the liturgy made it constantly spiral backward, rendering past sacred events present through ritual commemoration. Such liturgical celebration of time had many layers, mingled and arranged according to the calendar, with its varying and its fixed cycles of feasts, voiced through psalmody, readings from the Old and New Testaments and the lives of the saints.
How the past was known, both by individuals and within communities, varied from one specific local community to another, for the liturgy was ever changing, especially as new feasts, and feasts of new saints, were added to suit particular needs. Some knew about certain past events from what they read, as had long been the case, but in the Middle Ages many more knew about the past from various reenactments: ritual actions, dramatic productions, sermons and tales they heard about biblical characters and saints, encounters with art and architecture and from contact with shrines and relics.
Much of medieval history-making was thus memorial in nature, bringing the past forward, again and again, to recall its individual or communal significance. At the heart of the medieval Christian understanding of the past was a simple, foundational command from Christ: ‘Hoc facite in meam commemorationem’ [‘Do this in remembrance of me’] (Luke 22. 19).