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.
Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.
Methods:
This was a retrospective (2017–2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted.
Results:
Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting (r = 0.53, p < 0.0001) and peak stroke volume (r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse (r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume (Z-score –1.2 ± 1.3 vs. –0.36 ± 1.3, p = 0.01) and end-systolic volume (Z-score –1.0 ± 1.4 vs. −0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03).
Discussion:
Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.
Using information from all International Monetary Fund conditionality programmes from 1990 to 2018, we implement a dynamic Augmented Inverse Probability Weighting Regression Adjustment approach to enquire whether public-sector employment retrenchment may be incompatible with the goal of shrinking the informal economy. The estimated effect 5 years after the policy intervention indicates an increase in the share of the shadow economy to GDP by about 1.3 percentage points. More importantly, this change involves a sizable reallocation of private economic activity from its formal to its informal part; that is, the size of the formal private sector relative to the size of the informal sector decreases by seven percentage points. We interpret these findings through a two-sector model in which there is interdependence between worker incomes and the allocation of product demand across the formal and informal sectors.
Paediatric patients with heart failure requiring ventricular assist devices are at heightened risk of neurologic injury and psychosocial adjustment challenges, resulting in a need for neurodevelopmental and psychosocial support following device placement. Through a descriptive survey developed in collaboration by the Advanced Cardiac Therapies Improving Outcomes Network and the Cardiac Neurodevelopmental Outcome Collaborative, the present study aimed to characterise current neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices.
Method:
Members of both learning networks developed a 25-item electronic survey assessing neurodevelopmental and psychosocial care practices specific to paediatric ventricular assist device patients. The survey was sent to Advanced Cardiac Therapies Improving Outcomes Network site primary investigators and co-primary investigators via email.
Results:
Of the 63 eligible sites contacted, responses were received from 24 unique North and South American cardiology centres. Access to neurodevelopmental providers, referral practices, and family neurodevelopmental education varied across sites. Inpatient neurodevelopmental care consults were available at many centres, as were inpatient family support services. Over half of heart centres had outpatient neurodevelopmental testing and individual psychotherapy services available to patients with ventricular assist devices, though few centres had outpatient group psychotherapy (12.5%) or parent support groups (16.7%) available. Barriers to inpatient and outpatient neurodevelopmental care included limited access to neurodevelopmental providers and parent/provider focus on the child’s medical status.
Conclusions:
Paediatric patients with ventricular assist devices often have access to neurodevelopmental providers in the inpatient setting, though supports vary by centre. Strengthening family neurodevelopmental education, referral processes, and family-centred psychosocial services may improve current neurodevelopmental/psychosocial care for paediatric ventricular assist device patients.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Bioturbation can increase time averaging by downward and upward movements of young and old shells within the entire mixed layer and by accelerating the burial of shells into a sequestration zone (SZ), allowing them to bypass the uppermost taphonomically active zone (TAZ). However, bioturbation can increase shell disintegration concurrently, neutralizing the positive effects of mixing on time averaging. Bioirrigation by oxygenated pore-water promotes carbonate dissolution in the TAZ, and biomixing itself can mill shells weakened by dissolution or microbial maceration, and/or expose them to damage at the sediment–water interface. Here, we fit transition rate matrices to bivalve age–frequency distributions from four sediment cores from the southern California middle shelf (50–75 m) to assess the competing effects of bioturbation on disintegration and time averaging, exploiting a strong gradient in rates of sediment accumulation and bioturbation created by historic wastewater pollution. We find that disintegration covaries positively with mixing at all four sites, in accord with the scenario where bioturbation ultimately fuels carbonate disintegration. Both mixing and disintegration rates decline abruptly at the base of the 20- to 40-cm-thick, age-homogenized surface mixed layer at the three well-bioturbated sites, despite different rates of sediment accumulation. In contrast, mixing and disintegration rates are very low in the upper 25 cm at an effluent site with legacy sediment toxicity, despite recolonization by bioirrigating lucinid bivalves. Assemblages that formed during maximum wastewater emissions vary strongly in time averaging, with millennial scales at the low-sediment accumulation non-effluent sites, a centennial scale at the effluent site where sediment accumulation was high but bioturbation recovered quickly, and a decadal scale at the second high-sedimentation effluent site where bioturbation remained low for decades. Thus, even though disintegration rates covary positively with mixing rates, reducing postmortem shell survival, bioturbation has the net effect of increasing the time averaging of skeletal remains on this warm-temperate siliciclastic shelf.
This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.
Caribbean health research has overwhelmingly employed measures developed elsewhere and rarely includes evaluation of psychometric properties. Established measures are important for research and practice. Particularly, measures of stress and coping are needed. Stressors experienced by Caribbean people are multifactorial, as emerging climate threats interact with existing complex and vulnerable socioeconomic environments. In the early COVID-19 pandemic, our team developed an online survey to assess the well-being of health professions students across university campuses in four Caribbean countries. This survey included the Perceived Stress Scale, 10-item version (PSS-10) and the Brief Resilient Coping Scale (BRCS). The participants were 1,519 health professions students (1,144 females, 372 males). We evaluated the psychometric qualities of the measures, including internal consistency, concurrent validity by correlating both measures, and configural invariance using confirmatory factor analysis (CFA). Both scales had good internal consistency, with omega values of 0.91 for the PSS-10 and 0.81 for the BRCS. CFA suggested a two-factor structure of the PSS-10 and unidimensional structure of the BRCS. These findings support further use of these measures in Caribbean populations. However, the sampling strategy limits generalizability. Further research evaluating these and other measures in the Caribbean is desirable.
This position paper by the international IMMERSE consortium reviews the evidence of a digital mental health solution based on Experience Sampling Methodology (ESM) for advancing person-centered mental health care and outlines a research agenda for implementing innovative digital mental health tools into routine clinical practice. ESM is a structured diary technique recording real-time self-report data about the current mental state using a mobile application. We will review how ESM may contribute to (1) service user engagement and empowerment, (2) self-management and recovery, (3) goal direction in clinical assessment and management of care, and (4) shared decision-making. However, despite the evidence demonstrating the value of ESM-based approaches in enhancing person-centered mental health care, it is hardly integrated into clinical practice. Therefore, we propose a global research agenda for implementing ESM in routine mental health care addressing six key challenges: (1) the motivation and ability of service users to adhere to the ESM monitoring, reporting and feedback, (2) the motivation and competence of clinicians in routine healthcare delivery settings to integrate ESM in the workflow, (3) the technical requirements and (4) governance requirements for integrating these data in the clinical workflow, (5) the financial and competence related resources related to IT-infrastructure and clinician time, and (6) implementation studies that build the evidence-base. While focused on ESM, the research agenda holds broader implications for implementing digital innovations in mental health. This paper calls for a shift in focus from developing new digital interventions to overcoming implementation barriers, essential for achieving a true transformation toward person-centered care in mental health.
Landscapes are important frames for understanding and bridging environmental perspectives, including between Indigenous and scientific knowledge systems. Landscapes are both “natural” and “cultural,” for, as Indigenous societies attest, all landscapes manifest the coevolutionary interplay of human and nonhuman forces. We apply three integrated ecological lenses to analyze this interplay: historical ecology, ethno-ecology, and political ecology. Our case study is the Alsek-Dry Bay region of Southeast Alaska and Western Canada, at the intersection of the northern Tlingit and Athabaskan worlds. Historically an epicenter of astonishing geological dynamism and disruption, biological productivity and diversity, this landscape was also a mecca of cultural exchange, contestation, and appropriation. Ironically, the Alsek-Dry Bay landscape is now “preserved” as the center of a celebrated World Heritage Site based solely on its “natural” landscapes and “wilderness” character, and not for its Indigenous identity as a place of outstanding cultural significance – where the trickster-worldmaker Raven literally transformed the cosmos and topography – and the product of deep cultural-environmental histories. Bringing these ecological perspectives together enables a broader appreciation of the natural and cultural dynamism that has shaped such sites and of the enduring value and lessons of Indigenous knowledge systems that have coevolved with rapidly changing landscapes.
The 2022 Russian invasion of Ukraine was a watershed moment in European politics. The invasion prompted a massive influx of refugees into Central Europe, a region in which immigration has proven highly contentious and politically salient in recent decades. We study public opinion toward refugees in Hungary, a highly exclusionary political environment in which anti-migrant and anti-refugee sentiments are commonly invoked by the ruling government. Combining historical public opinion data from the past decade with two rounds of original survey data from 2022, we demonstrate that the Ukrainian refugee crisis was accompanied by a large increase in tolerance for refugees, reversing what had previously been one of the most anti-refugee public opinion environments in Europe. To explain this reversal, we use a series of survey experiments coupled with detailed settlement-level demographic data to investigate how conflict proximity and racial, religious, and national identity shape openness to refugees. We find that the distinguishing feature of the 2022 refugee crisis was that refugees were mostly white European Christians driven from their home country by conflict. We discuss the implications of our argument for Hungary, for European politics in times of crisis, and for the politics of public opinion in competitive authoritarian regimes.
OBJECTIVES/GOALS: Although the approval of immune checkpoint inhibitors (ICIs) revolutionized the treatment of metastatic breast cancer (BC), yet about 30% remain unresponsive. Since the potency of ICIs depends on the efficient presentation of tumor-specific antigens by cancer cells, compounds which increase such presentation could increase efficacy of ICIs. METHODS/STUDY POPULATION: A library of the ester and urethane derivatives of polyether ionophore antibiotic, monensin (MON) has been synthesized. MTT cell viability assays were performed on the panel of human and mouse BC cell lines, and non-cancerous breast epithelial cells to determine IC50 values of MON and its derivatives. Selectivity Indexes were calculated to identify the most selective compounds towards cancer versus non-cancer cells. Major Histocompatibility Complex (MHC) class I and II presentation and Programmed death-ligand 1 (PD-L1) expression have been determined using flow cytometry. Proteins involved in apoptosis, autophagy and immunogenic cell death were identified through immunoblotting. At least three biological replicates have been performed for each experiment. RESULTS/ANTICIPATED RESULTS: MON and several of its derivatives shown activity in nanomolar range against MDA-MB-231 human BC cell line. MON and its most potent derivatives significantly increased MHC class I and II presentation and downregulated the expression of PD-L1 in BC cell lines. DISCUSSION/SIGNIFICANCE: Present findings will lead to the development of new therapeutic approaches that can serve as single agents or be used in combination with existing ICIs for the treatment of metastatic BC. By pushing the boundaries of our understanding and developing new therapies, this research can make an impact in improving outcomes for patients with metastatic BC.
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
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.
Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:
High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:
Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:
Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
Understanding the dynamics of snow avalanches is crucial for predicting their destructive potential and mobility. To gain insight into avalanche dynamics at a particle level, the AvaNode in-flow sensor system was developed. These synthetic particles, equipped with advanced and affordable sensors such as an inertial measurement unit (IMU) and global navigation satellite system (GNSS), travel with the avalanche flow. This study focuses on assessing the feasibility of the in-flow measurement systems. The experiments were conducted during the winter seasons of 2021–2023, both in static snow cover and dynamic avalanche conditions of medium-sized events. Radar measurements were used in conjunction with the particle trajectories and velocities to understand the behaviour of the entire avalanche flow. The dynamic avalanche experiments allowed to identify three distinct particle flow states: (I) initial rapid acceleration, (II) a steady state flow with the highest velocities (9–17 ms−1), and (III) a longer deceleration state accompanied by the largest measured rotation rates. The particles tend to travel towards the tail of the avalanche and reach lower velocities compared to the frontal approach velocities deduced from radar measurements (ranging between 23–28 ms−1). The presented data give a first insight in avalanche particle measurements.
This chapter considers the music publishing industry in Puccini’s Italy, with a particular focus on Puccini’s principal publisher, the Casa Ricordi. The chapter examines the role that publishers played within the wider operatic industry, which by Puccini’s time included managing contracts between composers and opera houses and influencing casting, as well as the more traditional business of printing, publishing, and promoting scores. The particular musical specialisms of the Sonzogno and Ricordi publishing houses are discussed. The author shows how Ricordi elevated Puccini to the position of national-composer-elect towards the end of Verdi’s lifetime and constructed a ‘Puccini myth’. Expensive, sophisticated publicity tools and marketing strategies were used to promote Puccini’s works, not only in Italy but in territories across the globe. The chapter discusses how Puccini’s relationship with the firm changed as a result of the succession of power from Giulio to Tito Ricordi upon the former’s death, as well as the firm’s management of Puccini’s works after his own death.
This chapter examines Puccini’s relationship with early film. The composer’s career coincided with nearly the first thirty years of the cinematic art form, and it was a form of technology with which Puccini had an ambivalent relationship. The chapter begins with an account of Puccini’s known thoughts about film and cinema going. There follows an extensive discussion of Puccini’s and Ricordi’s legal efforts to prevent the use of his music as film accompaniment, and of the difficulty in recouping royalties. By the 1920s, however, Ricordi was including a clause about film usage in opera contracts, including that for Turandot. From the 1930s, with the arrival of the ‘talkies’, commercial opportunities became apparent and the company pursued a more liberal course. The chapter also considers how Puccini’s operas were brought to the screen during his lifetime and shortly after – there was a particular vogue for Tosca films – and discusses the ways in which the composer’s works might be considered ‘cinematic’.
To examine differences in noticing and use of nutrition information comparing jurisdictions with and without mandatory menu labelling policies and examine differences among sociodemographic groups.
Design:
Cross-sectional data from the International Food Policy Study (IFPS) online survey.
Setting:
IFPS participants from Australia, Canada, Mexico, United Kingdom and USA in 2019.
Participants:
Adults aged 18–99; n 19 393.
Results:
Participants in jurisdictions with mandatory policies were significantly more likely to notice and use nutrition information, order something different, eat less of their order and change restaurants compared to jurisdictions without policies. For noticed nutrition information, the differences between policy groups were greatest comparing older to younger age groups and comparing high education (difference of 10·7 %, 95 % CI 8·9, 12·6) to low education (difference of 4·1 %, 95 % CI 1·8, 6·3). For used nutrition information, differences were greatest comparing high education (difference of 4·9 %, 95 % CI 3·5, 6·4) to low education (difference of 1·8 %, 95 % CI 0·2, 3·5). Mandatory labelling was associated with an increase in ordering something different among the majority ethnicity group and a decrease among the minority ethnicity group. For changed restaurant visited, differences were greater for medium and high education compared to low education, and differences were greater for higher compared to lower income adequacy.
Conclusions:
Participants living in jurisdictions with mandatory nutrition information in restaurants were more likely to report noticing and using nutrition information, as well as greater efforts to modify their consumption. However, the magnitudes of these differences were relatively small.