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Randomized clinical trials (RCT) are the foundation for medical advances, but participant recruitment remains a persistent barrier to their success. This retrospective data analysis aims to (1) identify clinical trial features associated with successful participant recruitment measured by accrual percentage and (2) compare the characteristics of the RCTs by assessing the most and least successful recruitment, which are indicated by varying thresholds of accrual percentage such as ≥ 90% vs ≤ 10%, ≥ 80% vs ≤ 20%, and ≥ 70% vs ≤ 30%.
Data from the internal research registry at Columbia University Irving Medical Center and Aggregated Analysis of ClinicalTrials.gov were collected for 393 randomized interventional treatment studies closed to further enrollment. We compared two regularized linear regression and six tree-based machine learning models for accrual percentage (i.e., reported accrual to date divided by the target accrual) prediction. The outperforming model and Tree SHapley Additive exPlanations were used for feature importance analysis for participant recruitment. The identified features were compared between the two subgroups.
CatBoost regressor outperformed the others. Key features positively associated with recruitment success, as measured by accrual percentage, include government funding and compensation. Meanwhile, cancer research and non-conventional recruitment methods (e.g., websites) are negatively associated with recruitment success. Statistically significant subgroup differences (corrected p-value < .05) were found in 15 of the top 30 most important features.
This multi-source retrospective study highlighted key features influencing RCT participant recruitment, offering actionable steps for improvement, including flexible recruitment infrastructure and appropriate participant compensation.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5–11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29–3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
Previous research indicates that parental emotion socialization (ES) practices play important roles in adolescents’ social and emotional development. However, longitudinal studies testing bidirectional effects are relatively scarce. Additionally, most studies have focused on people from Western societies. In the current 3-year, multi-informant, longitudinal study of Chinese adolescents and their parents, we investigated prospective bidirectional effects between parental positive ES practices and adolescents’ psychosocial adjustment (i.e., self-esteem and depressive symptoms). Adolescents (N = 710 at T1, 50% boys, Mage = 12.41, SD = 0.59) reported on parental positive ES practices and their own depressive symptoms and self-esteem when they were in 7th, 8th, and 9th grade. Mothers and fathers reported on their own use of positive ES practices at all three time points. We utilized a random intercept cross-lagged panel model to examine between- and within-family effects. Overall results showed robust effects of adolescent depressive symptoms on parental positive ES practices and bidirectional effects between parental ES and adolescent self-esteem. Effects differed by informants whether using adolescent-perceived data, or mother- or father-reported data. However, these child effects and bidirectional effects did not differ by adolescent sex. Our findings add to the understanding of parental ES and adolescent psychosocial adjustment.
We aimed to examine the association between the quantity and quality of dietary fat in early pregnancy and gestational diabetes mellitus (GDM) risk. In total, 1477 singleton pregnant women were included from Sichuan Provincial Hospital for Women and Children, Southwest China. Dietary information was collected by a 3-d 24-h dietary recall. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to estimate relative risks (RR) and 95% CI. The results showed that total fat intake was positively associated with GDM risk (Q4 v. Q1: RR = 1·40; 95 % CI 1·11, 1·76; Ptrend = 0·001). This association was also observed for the intakes of animal fat and vegetable fat. After stratified by total fat intake (< 30 %E v. ≥ 30 %E), the higher animal fat intake was associated with higher GDM risk in the high-fat group, but the moderate animal fat intake was associated with reduced risk of GDM (T2 v. T1: RR = 0·65; 95 % CI 0·45, 0·96) in the normal-fat group. Vegetable fat intake was positively associated with GDM risk in the high-fat group but not in the normal-fat group. No association between fatty acids intakes and GDM risk was found. In conclusion, total fat, animal and vegetable fat intakes were positively associated with GDM risk, respectively. Whereas when total fat intake was not excessive, higher intakes of animal and vegetable fat were likely irrelevant with increased GDM risk, even the moderate animal fat intake could be linked to lower GDM risk.
This study examined the influences of coated folic acid (CFA) and coated riboflavin (CRF) on bull performance, nutrients digestion and ruminal fermentation. Forty-eight Angus bulls based on a randomised block and 2 × 2 factorial design were assigned to four treatments. The CFA of 0 or 6 mg of folic acid/kg DM was supplemented in diets with CRF 0 or 60 mg riboflavin (RF)/kg DM. Supplementation of CRF in diets with CFA had greater increase in daily weight gain and feed efficiency than in diets without CFA. Supplementation with CFA or CRF enhanced digestibility of DM, organic matter, crude protein, neutral-detergent fibre and non-fibre carbohydrate. Ruminal pH and ammonia N content decreased and total volatile fatty acids concentration and acetate to propionate ratio elevated for CFA or CRF addition. Supplement of CFA or CRF increased the activities of fibrolytic enzymes and the numbers of total bacteria, protozoa, fungi, dominant fibrolytic bacteria and Prevotella ruminicola. The activities of α-amylase, protease and pectinase and the numbers of Butyrivibrio fibrisolvens and Ruminobacter amylophilus were increased by CFA but were unaffected by CRF. Blood concentration of folate elevated and homocysteine decreased for CFA addition. The CRF supplementation elevated blood concentrations of folate and RF. These findings suggested that CFA or CRF inclusion had facilitating effects on performance and ruminal fermentation, and combined addition of CFA and CRF had greater increase in performance than CFA or CRF addition alone in bulls.
Almost all hospitals are equipped with air-conditioning systems to provide a comfortable environment for patients and staff. However, the accumulation of dust and moisture within these systems increases the risk of transmission of microbes and have on occasion been associated with outbreaks of infection. Nevertheless, the impact of air-conditioning on the transmission of microorganisms leading to infection remains largely uncertain. We conducted a scoping review to screen systematically the evidence for such an association in the face of the coronavirus disease 2019 epidemic. PubMed, Embase and Web of Science databases were explored for relevant studies addressing microbial contamination of the air, their transmission and association with infectious diseases. The review process yielded 21 publications, 17 of which were cross-sectional studies, three were cohort studies and one case−control study. Our analysis showed that, compared with naturally ventilated areas, microbial loads were significantly lower in air-conditioned areas, but the incidence of infections increased if not properly managed. The use of high-efficiency particulate air (HEPA) filtration not only decreased transmission of airborne bioaerosols and various microorganisms, but also reduced the risk of infections. By contrast, contaminated air-conditioning systems in hospital rooms were associated with a higher risk of patient infection. Cleaning and maintenance of such systems to recommended standards should be performed regularly and where appropriate, the installation of HEPA filters can effectively mitigate microbial contamination in the public areas of hospitals.
Household entrepreneurship is a basic unit of entrepreneurial activity, and a crucial aspect of connecting personal and social wellbeing. This study examines the relationship between the proportion of elderly family members and household entrepreneurship. This study also assesses the mediating effect of the middle-aged generation's support to their parents and the moderating effect of the parents’ support with respect to the proportion of elderly family members and entrepreneurship. We use data from the China Family Panel Studies. We adopt the instrumental variable method to deal with endogeneity, robustness and credibility of the estimation results. The results show that a higher proportion of elderly family members impedes household entrepreneurship. Moreover, the financial and instrumental support provided by the middle-aged generation to their parents significantly mediates the relationship between the proportion of elderly family members and household entrepreneurship. In turn, parents’ financial support to the middle-aged generation moderates the focal relationship; however, parents’ instrumental support does not moderate the focal relationship. These findings emphasise the need to develop a comprehensive social security network for older adults that will indirectly promote household entrepreneurship, and improve personal and social wellbeing.
To investigate the influences of cobalt (Co) and folic acid (FA) on growth performance and rumen fermentation, Holstein male calves (n 40) were randomly assigned to four groups according to their body weights. Cobalt sulphate at 0 or 0·11 mg Co/kg DM and FA at 0 or 7·2 mg/kg DM were used in a 2 × 2 factorial design. Average daily gain was elevated with FA or Co supplementation, but the elevation was greater for supplementing Co in diets without FA than with FA. Supplementing FA or Co increased DM intake and total-tract nutrient digestibility. Rumen pH was unaltered with FA but reduced with Co supplementation. Concentration of rumen total volatile fatty acids was elevated with FA or Co inclusion. Acetate percentage and acetate to propionate ratio were elevated with FA inclusion. Supplementing Co decreased acetate percentage and increased propionate percentage. Activities of xylanase and α-amylase and populations of total bacteria, fungi, protozoa, Ruminococcus albus, Fibrobacter succinogenes and Prevotella ruminicola increased with FA or Co inclusion. Activities of carboxymethyl-cellulase and pectinase increased with FA inclusion and population of methanogens decreased with Co addition. Blood folates increased and homocysteine decreased with FA inclusion. Blood glucose and vitamin B12 increased with Co addition. The data suggested that supplementing 0·11 mg Co/kg DM in diets containing 0·09 mg Co/kg DM increased growth performance and nutrient digestibility but had no improvement on the effects of FA addition in calves.
The Upper Triassic Xujiahe Formation is a typical tight gas reservoir in which natural fractures determine the migration, accumulation and production capacity of tight gas. In this study, we focused on the influences of natural fractures on the tight gas migration and production. We clarified characteristics and attributes (i.e. dips, apertures, filling degree and cross-cutting relationships) of the fractures based on image logging interpretations and core descriptions. Previous studies of electron spin resonance, carbon and oxygen isotopes, homogenization temperature of fluid inclusions analysis and basin simulation were considered. This study also analysed the fracture sequences, source of fracture fillings, diagenetic sequences and tight gas enrichment stages. We obtained insight into the relationship between fracture evolution and hydrocarbon charging, particularly the effect of the apertures and intensity of natural fractures on tight gas production. We reveal that the bedding fractures are short horizontal migration channels of tight gas. The tectonic fractures with middle, high and nearly vertical angles are beneficial to tight gas vertical migration. The apertures of fractures are controlled by the direction of maximum principal stress and fracture angle. The initial gas production of the vertical wells presents a positive correlation with the fracture abundance, and the intensity and aperture of fractures are the fundamental factors that determine the tight gas production. With these findings, this study is expected to guide the future exploration and development of tight gas with similar geological backgrounds.
Extreme wave runup around a simplified representative floating production, storage and offloading vessel hull with a vertical bow is studied using computational fluid dynamics, complemented by experimental and diffraction analysis. This is a highly nonlinear system involving large vessel motions and extreme surface waves, and the behaviour is important for offshore design and operations. A separation method based on phase manipulation is carried out to facilitate the extraction of harmonics associated with the Stokes expansion of nonlinear waves. The separation method is applied to numerical and experimental data, and found to work well even for a highly nonlinear wave field scattered from a freely floating ship-shaped body. It is found that both low- and high-frequency second harmonic components can lead to wave runup at significantly higher levels than predicted by a linear analysis, while the vessel motions are very close to linear. The nonlinearity in the local wave field rather than vessel motion is key for the excitation of nonlinear extreme runup.
Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.
We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS).
In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200–400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup).
Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS.
Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case–control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.
Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression.
A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE.
Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores.
This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.
Vetulicolians are a group of exclusively Cambrian animals characterized by an anterior section with lateral pouches and a posterior section that appears segmented. The precise phylogenetic affinity of vetulicolians is debated because there is a lack of consensus regarding the interpretation of their anatomical features. Their disparate morphology might even cause one to question whether this is a monophyletic taxon. In total, there are 15 species grouped into three families included in vetulicolians. Here we focus on new specimens of Yuyuanozoon magnificissimi Chen, Feng, and Zhu in Chen et al., 2003, a species that was first described from only a single specimen from the Chengjiang Biota (Cambrian Series 2, Stage 3, Eoredlichia-Wutingaspis trilobite Biozone), Yunnan Province, China. The species is notable in being exceptionally large (up to 20 cm long). Morphological observations on the new specimens clarify the nature of the wide circular opening at the presumed anterior end of the animal and the cowl-shaped lateral openings within this anterior section. Taphonomic observations identify wrinkles in the anterior section and twists in the posterior segmented section. In particular, the shape of the anterior opening of Yuyuanozoon magnificissimi suggests significant differences from other vetulicolians. Taxonomic reappraisal of Y. magnificissimi indicates that it belongs within the family Didazoonidae, as that is presently defined.
Neoseiulus barkeri (HUGHES) is the natural enemy of spider mites, whiteflies and thrips. Screening for chemically-resistant predatory mites is a practical way to balance the contradiction between the pesticide using and biological control. In this study, the number of eggs laid by fenpropathrin-susceptible and resistant strains of N. barkeri was compared. Additionally, we cloned three N. barkeri vitellogenin (Vg) genes and used quantitative real-time polymerase chain reaction to quantify Vg expression in susceptible and resistant strains. The total number of eggs significantly increased in the fenpropathrin-resistant strain. The full-length cDNA cloning of three N. barkeri Vg genes (NbVg1, NbVg2 and NbVg3) revealed that the open reading frames of NbVg1, NbVg2 and NbVg3 were 5571, 5532 and 4728 bp, encoding 1856, 1843 and 1575 amino acids, respectively. The three N. barkeri Vg possessed the Vitellogenin-N domain (or lipoprotein N-terminal domain (LPD_N)), von Willebrand factor type D domain (VWD) and the domain with unknown function 1943 (DUF1943). The NbVg1 and NbVg2 expression levels were significantly higher in the resistant strain than in the susceptible strain, while the NbVg3 expression level was lower in the resistant strain. Thus, we speculate that the increased number of eggs laid by the fenpropathrin-resistant strain of N. barkeri may be a consequence of changes in Vg gene expression.
We investigate a degenerate parabolic variational inequality arising from optimal continuous exercise perpetual executive stock options. It is also shown in Qin et al. (Continuous-Exercise Model for American Call Options with Hedging Constraints, working paper, available at SSRN: http://dx.doi.org/10.2139/ssrn.2757541) that to make this problem non-trivial the stock's growth rate must be no smaller than the discount rate. Well-posedness of the problem is established in Lai et al. (2015, Mathematical analysis of a variational inequality modeling perpetual executive stock options, Euro. J. Appl. Math., 26 (2015), 193–213), Qin et al. (2015, Regularity free boundary arising from optimal continuous exercise perpetual executive stock options, Interfaces and Free Boundaries, 17 (2015), 69–92), Song & Yu (2011, A parabolic variational inequality related to the perpetual American executive stock options, Nonlinear Analysis, 74 (2011), 6583-6600) for the case when the underlying stock's expected return rate is smaller than the discount rate. In this paper, we consider the remaining case: the discount rate is bigger than the growth rate but no bigger than the return rate. The existence of a unique classical solution as well as a continuous and strictly decreasing free boundary is proved.
The recently described radiodontan Lyrarapax unguispinus Cong et al., 2014 from the Chengjiang biota (Cambrian Series 2, Stage 3) highlighted a new morphological type of frontal appendage and unique mouth structures, a functional combination reinforcing the diversification of feeding strategies of radiodontans during the early Cambrian. Here we describe Lyrarapax trilobus n. sp. from the same fossil Konservat-Lagerstätte. The new species differs from L. unguispinus in the morphology and distribution of endites on the frontal appendage and the strengthening structure of the body flaps. The two species resemble each other in body shape (pattern of flap size), neck segment number, cephalic plates, and most importantly a mouth characterized by concentric wrinkled furrows. The latter confirms that a soft mouth without sclerotized plates is a real feature of Lyrarapax and supports the idea that oral structures provide valid diagnostic characters within Radiodonta.