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In the UK, around 1 in 4 adults over 65 years suffers from depression. Depression case finding followed by alerting patients and their general practioners (GPs) (screening + GP) is a promising strategy to facilitate depression management, but its cost-effectiveness remains unclear.
Aims
To investigate the cost-effectiveness of screening + GP compared with standard of care (SoC) in northern England.
Method
Conducted alongside the CASCADE study, 1020 adults aged 65+ years were recruited. Participants with baseline Geriatric Depression Scale (GDS) ≥5 were allocated to the intervention arm and those >5 to SoC. Resource use and EQ-5D-5L data were collected at baseline and 6 months. Incremental cost-effectiveness ratio was calculated. Non-parametric bootstrapping was performed to capture sampling uncertainty. The results are presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted to assess the robustness of primary findings. Subgroup analyses were undertaken to examine the cost-effectiveness among participants with more comparable baseline characteristics across treatment groups.
Results
Screening + GP incurred £37 more costs and 0.006 fewer quality-adjusted life years than SoC; the probability of the former being cost-effective was <5% at a £30 000 cost-effectiveness threshold. Sensitivity analyses confirmed the base-case findings. Subgroup analyses indicated that screening + GP was cost-effective when patients with baseline GDS 2–7, 3–6 and 4–5, respectively, were analysed.
Conclusions
Screening + GP was dominated by SoC in northern England. However, subgroup analyses suggested it could be cost-effective if patients with more balanced baseline characteristics were analysed. Economic evaluations alongside randomised controlled trials are warranted to validate these findings.
Advances in incremental Datalog evaluation strategies have made Datalog popular among use cases with constantly evolving inputs such as static analysis in continuous integration and deployment pipelines. As a result, new logic programming debugging techniques are needed to support these emerging use cases.
This paper introduces an incremental debugging technique for Datalog, which determines the failing changes for a rollback in an incremental setup. Our debugging technique leverages a novel incremental provenance method. We have implemented our technique using an incremental version of the Soufflé Datalog engine and evaluated its effectiveness on the DaCapo Java program benchmarks analyzed by the Doop static analysis library. Compared to state-of-the-art techniques, we can localize faults and suggest rollbacks with an overall speedup of over 26.9$\times$ while providing higher quality results.
To introduce the Emory 10-element Complex Figure (CF) scoring system and recognition task. We evaluated the relationship between Emory CF scoring and traditional Osterrieth CF scoring approach in cognitively healthy volunteers. Additionally, a cohort of patients undergoing deep brain stimulation (DBS) evaluation was assessed to compare the scoring methods in a clinical population.
Method:
The study included 315 volunteers from the Emory Healthy Brain Study (EHBS) with Montreal Cognitive Assessment (MoCA) scores of 24/30 or higher. The clinical group consisted of 84 DBS candidates. Scoring time differences were analyzed in a subset of 48 DBS candidates.
Results:
High correlations between scoring methods were present for non-recognition components in both cohorts (EHBS: Copy r = 0.76, Immediate r = 0.86, Delayed r = 0.85, Recognition r = 47; DBS: Copy r = 0.80, Immediate r = 0.84, Delayed Recall r = 0.85, Recognition r = 0.37). Emory CF scoring times were significantly shorter than Osterrieth times across non-recognition conditions (all p < 0.00001, individual Cohen’s d: 1.4–2.4), resulting in an average time savings of 57%. DBS patients scored lower than EHBS participants across CF memory measures, with larger effect sizes for Emory CF scoring (Cohen’s d range = 1.0–1.2). Emory CF scoring demonstrated better group classification in logistic regression models, improving DBS candidate classification from 16.7% to 32.1% compared to Osterrieth scoring.
Conclusions:
Emory CF scoring yields results that are highly correlated with traditional Osterrieth scoring, significantly reduces scoring time burden, and demonstrates greater sensitivity to memory decline in DBS candidates. Its efficiency and sensitivity make Emory CF scoring well-suited for broader implementation in clinical research.
Background: External comparisons of antimicrobial use (AU) may be more informative if adjusted for encounter characteristics. Optimal methods to define input variables for encounter-level risk-adjustment models of AU are not established. Methods: This retrospective analysis of electronic health record data included 50 US hospitals in 2020-2021. We used NHSN definitions for all antibacterials days of therapy (DOT), including adult and pediatric encounters with at least 1 day present in inpatient locations. We assessed 4 methods to define input variables: 1) diagnosis-related group (DRG) categories by Yu et al., 2) adjudicated Elixhauser comorbidity categories by Goodman et al., 3) all Clinical Classification Software Refined (CCSR) diagnosis and procedure categories, and 4) adjudicated CCSR categories where codes not appropriate for AU risk-adjustment were excluded by expert consensus, requiring review of 867 codes over 4 months to attain consensus. Data were split randomly, stratified by bed size as follows: 1) training dataset including two-thirds of encounters among two-thirds of hospitals; 2) internal testing set including one-third of encounters within training hospitals, and 3) external testing set including the remaining one-third of hospitals. We used a gradient-boosted machine (GBM) tree-based model and two-staged approach to first identify encounters with zero DOT, then estimate DOT among those with >0.5 probability of receiving antibiotics. Accuracy was assessed using mean absolute error (MAE) in testing datasets. Correlation plots compared model estimates and observed DOT among testing datasets. The top 20 most influential variables were defined using modeled variable importance. Results: Our datasets included 629,445 training, 314,971 internal testing, and 419,109 external testing encounters. Demographic data included 41% male, 59% non-Hispanic White, 25% non-Hispanic Black, 9% Hispanic, and 5% pediatric encounters. DRG was missing in 29% of encounters. MAE was lower in pediatrics as compared to adults, and lowest for models incorporating CCSR inputs (Figure 1). Performance in internal and external testing was similar, though Goodman/Elixhauser variable strategies were less accurate in external testing and underestimated long DOT outliers (Figure 2). Agnostic and adjudicated CCSR model estimates were highly correlated; their influential variables lists were similar (Figure 3). Conclusion: Larger numbers of CCSR diagnosis and procedure inputs improved risk-adjustment model accuracy compared with prior strategies. Variable importance and accuracy were similar for agnostic and adjudicated approaches. However, maintaining adjudications by experts would require significant time and potentially introduce personal bias. If findings are confirmed, the need for expert adjudication of input variables should be reconsidered.
Disclosure: Elizabeth Dodds Ashley: Advisor- HealthTrackRx. David J Weber: Consultant on vaccines: Pfizer; DSMB chair: GSK; Consultant on disinfection: BD, GAMA, PDI, Germitec
Lynchets, often the defining component of historic agricultural landscapes in northern Europe, are generally associated with soft-limestone geologies and are particularly well developed on loess-mantled landscapes. To understand their formation and chronology, the authors present their geoarchaeological analyses of lynchet soils and loess deposits at Blick Mead and Charlton Forest in southern England, and Sint Martens-Voeren in Belgium. The lynchets date from the late prehistoric to the medieval periods and were constructed by plough action at the English sites, and by both cut-and-fill and ploughing in Belgium. This has resulted in the preservation of highly fertile loessic soils across chalk slopes, lost elsewhere. Although each example is associated with local/regional agricultural histories, the lynchets’ effective soil-retention capacities allowed them to survive as important heritage features with environmental benefits over millennia.
Some U.S. firms have women directors and executives, while many do not. We seek to explain this heterogeneity. Using U.S. Census data from 1900, we find that U.S. counties with populations originating from countries with stronger gender-egalitarian beliefs have more women in the labor market and in STEM occupations, and lower gender-pay gaps. Firms headquartered in such counties have more women executives and directors. When firms move to more gender-egalitarian counties, the representation of women on board increases. Our findings are consistent with the idea that inherited beliefs about gender roles impact the labor market and corporate leadership.
Terracing is found widely in the Mediterranean and in other hilly and mountainous regions of the world. Yet while archaeological attention to these ‘mundane’ landscape features has grown, they remain understudied, particularly in Northern Europe. Here, the authors present a multidisciplinary study of terraces in the Breamish Valley, Northumberland. The results date their construction to the Early to Middle Bronze Age, when they were built by cutting back the hillside, stone clearance and wall construction. Environmental evidence points to their use for cereal cultivation. The authors suggest that the construction and use of these terraces formed part of an Early to Middle Bronze Age agricultural intensification, which may have been both demographically and culturally driven.
With economic reform, in China, labour turnover of seafarers became more possible. However, little attention has been paid to its consequences. A limited literature indicates that Chinese seafarers may leave state-owned enterprises to become freelance seafarers, working in the global labour market for better wages and employment conditions. There have been predictions of a substantial increase in seafarer export, with China becoming the top labour supplier to the global maritime industry. However, such expectations have been largely unmet. Through 157 qualitative interviews with seafarers and managers in Chinese ship crewing agencies, we explore some reasons why this may be so. The findings suggest that Chinese seafarers are in fact limited in their willingness and ability to leave their companies. This is due to a complex mixture of organisational, regulatory, infrastructural and personal contexts that are their everyday experience of work in China. Analysis further suggests that the underdevelopment of a national regulatory infrastructure and welfare support mechanism for seafarers, along with poor implementation of the Maritime Labour Convention 2006, combine to limit the extent of the reform of the Chinese seafaring labour market. Together, these factors help to explain why China’s seafaring labour export has been far lower than anticipated.
Background: Povidone-iodine and chlorhexidine gluconate are commonly used antiseptics that have broad antiviral properties, including against SARS-CoV-2. Nasal and oral antisepsis is a possible option to reduce viral transmission; however, effectiveness data are limited. The acceptability of this method for adjunct infection control is also unknown. We are conducting a clinical randomized controlled trial (NCT04478019) to evaluate the effectiveness and feasibility of nasal and oral antisepsis to prevent COVID-19. Methods: Healthcare and other essential workers with in-person job duties were recruited into a 10-week clinical trial. Participation did not require in-person activities: all communication was web- or telephone-based, supplies were shipped directly to the participant, and participants self-collected specimens. Participants completed a 3-week intervention and 3-week control phases and were randomized to the timing of these phases (Fig. 1). During the 3-week intervention phase, participants applied povidone-iodine nasal swabs 2 times per day and chlorhexidine gluconate oral rinse 4 times per day following the manufacturers’ instructions for use. Participants continued all usual infection control measures (eg, face masks, eye protection, gowns, hand hygiene) as required by their workplace. To measure effectiveness against viral transmission, participants collected midturbinate nasal swabs 3 times per week to measure SARS-CoV-2 viral load. Participants also self-reported COVID-19 tests they received and why (eg, symptoms or exposure). To assess acceptability, participants completed pre- and post-surveys about their perceived and actual experience with the interventions. Participants also self-reported adverse effects due to the intervention. Results: As of December 3, 2021, 221 participants (148 healthcare workers and 73 non–healthcare essential workers) had enrolled. Moreover, 20 adverse effects have been reported, including skin irritation, epistaxis, and mouth discoloration; 9 participants withdrew due to side effects. Laboratory analyses are ongoing to measure effectiveness in reducing SARS-CoV-2 viral load. We performed an interim analysis of intervention acceptability. Survey responses were given on a Likert scale of 1 (not at all) to 5 (extremely). Although 36% of respondents (n = 74) reported on the postsurvey that the intervention was less acceptable than they had expected on the presurvey, the overall acceptability measure was still relatively high (3.76) (Fig. 2). In addition, 76% of respondents reported that they would use the intervention in the future (n = 56). Conclusions: Participant recruitment is ongoing, and data continue to be collected to analyze effectiveness and feasibility. Preliminary data suggest that participants find the nasal and oral antisepsis intervention to be an acceptable option to complement standard infection control methods to prevent COVID-19.
Funding: Professional Disposables International, Healthcare Division (PDIHC)
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Methods
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
Results
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
Conclusions
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Overseas study is a global phenomenon and a major business internationally. But does overseas study pay off? Using data from the 2015 China Household Finance Survey (CHFS), we examine the labour market performance of overseas returnees in China. To obtain more accurate results, we matched each returnee with a local so that the domestic group is as similar as possible to the returnee group. We then conducted empirical analyses of the matched data. We find that compared with domestic postgraduates, returnee postgraduates earn about 20 per cent more annually. Moreover, the salary premiums paid for foreign graduate degrees can be attributed principally to the superior human capital gained from overseas education rather than from any “signalling” effect. Also, returnees with graduate degrees are more likely to enter high-income professions and foreign-funded ventures, and to reach higher positions in those organizations. However, we find no significant differences in income, occupation choices and positions between returnee and local bachelor's degree recipients. As such, we suggest that Chinese students and their families are best served when the students obtain a local undergraduate degree and then go overseas for graduate training.
In this paper, we present a reanalysis of the silicon He-$\mathrm{\alpha}$ X-ray spectrum emission in Fujioka et al.’s 2009 photoionization experiment. The computations were performed with our radiative-collisional code, RCF. The central ingredients of our computations are accurate atomic data, inclusion of satellite lines from doubly excited states and accounting for the reabsorption of the emitted photons on their way to the spectrometer. With all these elements included, the simulated spectrum turns out to be in good agreement with the experimental spectrum.
OBJECTIVES/GOALS: Lack of blood vessels remains a major obstacle in tissue regeneration. Angiopoietin 1 and 2 modulate angiogenesis through the Tie2 receptor tyrosine kinase. Ang1 activates pAKT to promote endothelial cell survival while Ang2 antagonizes these effects. We aim to dissect the Ang/Tie2 pathway to uncover the molecular basis for these opposing effects. METHODS/STUDY POPULATION: Ang1 and Ang2 bind Tie2 via nearly identical F-domains (Fd). To investigate the molecular basis regulating the Tie2 pathway, we generated a series of computationally designed self-assembling protein scaffolds presenting F-domains in a wide range of valencies and geometries using Rosette Molecular Modeling Suite. We examined the protein kinase activation, cell migration, and blood vessel formation produced by the designed proteins in human umbilical vein endothelial cells. RESULTS/ANTICIPATED RESULTS: Two phenotypic classes were demonstrated by the number of presented F domains: scaffolds presenting 3 or 4 Fd have Ang2 like activity, upregulating pFAK and pERK but not pAKT and failing to induce cell migration and tube formation; scaffolds presenting more than 6 Fd have Ang1 like activity, upregulating the three signaling branches and enhancing cell migration and tube formation. Scaffolds with 8 or more Fd show superagonist activity, producing significantly stronger phenotypes than Ang1. These results suggest that Fd valency largely determines Ang1 vs Ang2 signaling outcomes, and our designed superagonists can outperform Ang1 in vascularization and wound healing. In in vivo experiments, nanoparticles displaying 60 copies of Fd produce significant revascularization in hemorrhagic brains. DISCUSSION/SIGNIFICANCE OF IMPACT: Targeting the Tie2 pathway is a new paradigm in regenerative medicine. Our designed constructs will enable us to generate high-affinity Tie2 agonists and antagonists as drugs to control angiogenesis, enabling tissue regeneration that recapitulates the biological architecture of the native tissue physiology, improving organ transplant outcome.
Porous metals represent a class of materials where the interplay of ligament length, width, node structure, and local geometry/curvature offers a rich parameter space for the study of critical length scales on mechanical behavior. Colloidal crystal templating of three-dimensionally ordered macroporous (3DOM, i.e., inverse opal) tungsten provides a unique structure to investigate the mechanical behavior at small length scales across the brittle–ductile transition. Micropillar compression tests show failure at 50 MPa contact pressure at 30 °C, implying a ligament yield strength of approximately 6.1 GPa for a structure with 5% relative density. In situ SEM frustum indentation tests with in-plane strain maps perpendicular to loading indicate local compressive strains of approximately 2% at failure at 30 °C. Increased sustained contact pressure is observed at 225 °C, although large (20%) nonlocal strains appear at 125 °C. The elevated-temperature mechanical performance is limited by cracks that initiate on planes of greatest shear under the indenter.
Freshwater habitats in China are potentially suitable for invasive alien turtle species and, consequently, raising turtles in aquaculture facilities and the trade in turtles this supplies pose risks to habitats and native wetland communities when exotic turtles escape or are released deliberately. Online trade (e-commerce) is making an increasing contribution to turtle sales in China, seemingly driving demand and thus potentially exacerbating the risk of release. We document the scale and spatial pattern of online sales of non-native turtles over 90 days on China's Taobao.com e-commerce site. The majority of sales were in the ecologically sensitive middle and lower Yangtze river basin (82.35% of > 840,000 slider turtles Trachemys scripta elegans, and 68.26% of > 100,000 snapping turtles, Chelydridae spp.). These species are native to the Americas. Concurrently, over 2008–2018, we found 104 mentions of feral turtle issues listed on Baidu News where, among the 53 prefectures mentioned, issues with invasive turtle populations also focused predominantly in the middle and lower Yangtze river basin. Although circumstantial, this association suggests that the substantial online sale of alien turtles could be having detrimental effects in China's Yangtze river basin. It is important to safeguard these wetland habitats, which are of global importance, by improving policies for detecting and regulating invasive alien turtle issues and by warning consumers about the ecological hazard of their purchases.
We report a facile method to fabricate CuNi nano-octahedra and nanocubes using a colloidal synthesis approach. The CuNi nanocrystals terminated with exclusive crystallographic facets were controlled and achieved by a group of synergetic capping ligands in a hot solution system. Specifically, the growth of {111}-bounded CuNi nano-octahedra is derived by a thermodynamic control, whereas the generation of {100}-terminated CuNi nanocubes is steered by a kinetic capping of chloride. Using a reduction of 4-nitrophenol with sodium borohydride as a model reaction, CuNi nano-octahedra and nanocubes demonstrated a strong facet-dependence due to their different surface energies although both exhibited remarkable catalytic activity with the high rate constant over mass (k/m). A kinetic study indicated that this is a pseudo first-order reaction with an excess of sodium borohydride. CuNi nanocubes as the catalysts showed better catalytic performance (k/m = 385 s-1•g-1) than the CuNi nano-octahedra (k/m = 120 s-1•g-1), indicating that 4-nitrophenol and hydrogen were adsorbed on the {100} facets with their molecules parallel to the surface much easier than those on {111} facets.
Ferroelectrics and related materials (e.g., non-traditional ferroelectrics such as relaxors) have long been used in a range of applications, but with the advent of new ways of modeling, synthesizing, and characterizing these materials, continued access to astonishing breakthroughs in our fundamental understanding come each year. While we still rely on these materials in a range of applications, we continue to re-write what is possible to be done with them. In turn, assumptions that have underpinned the use and design of certain materials are progressively being revisited. This perspective aims to provide an overview of the field of ferroelectric/relaxor/polar-oxide thin films in recent years, with an emphasis on emergent structure and function enabled by advanced synthesis, processing, and computational modeling.
Wildlife is an essential component of all ecosystems. Most places in the globe do not have local, timely information on which species are present or how their populations are changing. With the arrival of new technologies, camera traps have become a popular way to collect wildlife data. However, data collection has increased at a much faster rate than the development of tools to manage, process and analyse these data. Without these tools, wildlife managers and other stakeholders have little information to effectively manage, understand and monitor wildlife populations. We identify four barriers that are hindering the widespread use of camera trap data for conservation. We propose specific solutions to remove these barriers integrated in a modern technology platform called Wildlife Insights. We present an architecture for this platform and describe its main components. We recognize and discuss the potential risks of publishing shared biodiversity data and a framework to mitigate those risks. Finally, we discuss a strategy to ensure platforms like Wildlife Insights are sustainable and have an enduring impact on the conservation of wildlife.