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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.
We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP).
Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child’s gender, child’s birth year, mother’s birth year and child’s first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression.
The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07–9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10–2.39). Raised risks of perinatal morbidities and congenital anomalies were also found.
Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.
This study examines the individual and combined association of BMI and waist-to-hip ratio (WHR) with CVD risk using genetic scores of the obesity measurements as proxies.
A 2 × 2 factorial analysis approach was applied, with participants divided into four groups of lifetime exposure to low BMI and WHR, high BMI, high WHR, and high BMI and WHR based on weighted genetic risk scores. The difference in CVD risk across groups was evaluated using multivariable logistic regression.
A total of 408 003 participants were included from the prospective observational UK Biobank study.
A total of 58 429 CVD events were recorded. Compared to the low BMI and WHR genetic scores group, higher BMI or higher WHR genetic scores were associated with an increase in CVD risk (high WHR: OR, 1·07; 95 % CI (1·04, 1·10)); high BMI: OR, 1·12; 95 % CI (1·09, 1·16). A weak additive effect on CVD risk was found between BMI and WHR (high BMI and WHR: OR, 1·16; 95 % CI (1·12, 1·19)). Subgroup analysis showed similar patterns between different sex, age (<65, ≥65 years old), smoking status, Townsend deprivation index, fasting glucose level and medication uses, but lower systolic blood pressure was associated with higher CVD risk in obese participants.
High BMI and WHR were associated with increased CVD risk, and their effects are weakly additive. Even though there were overlapping of effect, both BMI and WHR are important in assessing the CVD risk in the general population.
More than one-half of betel-quid (BQ) chewers have betel-quid use disorder (BUD). However, no medication has been approved. We performed a randomised clinical trial to test the efficacy of taking escitalopram and moclobemide antidepressants on betel-quid chewing cessation (BQ-CC) treatment.
We enrolled 111 eligible male BUD patients. They were double-blinded, placebo-controlled and randomised into three treatment groups: escitalopram 10 mg/tab daily, moclobemide 150 mg/tab daily and placebo. Patients were followed-up every 2 weeks and the length of the trial was 8 weeks. The primary outcome was BQ-CC, defined as BUD patients who continuously stopped BQ use for ⩾6 weeks. The secondary outcomes were the frequency and amount of BQ intake, and two psychological rating scales. Several clinical adverse effects were measured during the 8-week treatment.
Intention-to-treat analysis shows that after 8 weeks, two (5.4%), 13 (34.2%) and 12 (33.3%) of BUD patients continuously quit BQ chewing for ⩾6 weeks among placebo, escitalopram, moclobemide groups, respectively. The adjusted proportion ratio of BQ-CC was 6.3 (95% CI 1.5–26.1) and 6.8 (95% CI 1.6–28.0) for BUD patients who used escitalopram and moclobemide, respectively, as compared with those who used placebo. BUD patients with escitalopram and moclobemide treatments both exhibited a significantly lower frequency and amount of BQ intake at the 8th week than those with placebo.
Prescribing a fixed dose of moclobemide and escitalopram to BUD patients over 8 weeks demonstrated treatment benefits to BQ-CC. Given a relatively small sample, this study provides preliminary evidence and requires replication in larger trials.
The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD.
After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions.
Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype.
A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.
Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations.
The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).
Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group.
Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype.
Improvement of environmental cleaning in hospitals has been shown to decrease in-hospital cross transmission of pathogens. Several objective methods, including aerobic colony counts (ACCs), the adenosine triphosphate (ATP) bioluminescence assay, and the fluorescent marker method have been developed to assess cleanliness. However, the standard interpretation of cleanliness using the fluorescent marker method remains uncertain.
To assess the fluorescent marker method as a tool for determining the effectiveness of hospital cleaning.
A prospective survey study.
An academic medical center.
The same 10 high-touch surfaces were tested after each terminal cleaning using (1) the fluorescent marker method, (2) the ATP assay, and (3) the ACC method. Using the fluorescent marker method under study, surfaces were classified as totally clean, partially clean, or not clean. The ACC method was used as the standard for comparison.
According to the fluorescent marker method, of the 830 high-touch surfaces, 321 surfaces (38.7%) were totally clean (TC group), 84 surfaces (10.1%) were partially clean (PC group), and 425 surfaces (51.2%) were not clean (NC group). The TC group had significantly lower ATP and ACC values (mean ± SD, 428.7 ± 1,180.0 relative light units [RLU] and 15.6 ± 77.3 colony forming units [CFU]/100 cm2) than the PC group (1,386.8 ± 2,434.0 RLU and 34.9 ± 87.2 CFU/100 cm2) and the NC group (1,132.9 ± 2,976.1 RLU and 46.8 ± 119.2 CFU/100 cm2).
The fluorescent marker method provided a simple, reliable, and real-time assessment of environmental cleaning in hospitals. Our results indicate that only a surface determined to be totally clean using the fluorescent marker method could be considered clean.
The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk.
The PubMed and EMBASE databases were searched. A dose–response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values.
The meta-analysis included seventeen studies.
A total of 10 601 patients.
The non-linear dose–response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose–response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187).
Our meta-analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only.
Video streaming over mobile wireless networks is getting popular in recent years. High video quality relies on large bandwidth provisioning, however, it decreases the number of supported users in wireless networks. Thus, effective bandwidth utilization becomes a crucial issue in wireless network as the bandwidth resource in wireless environment is precious and limited. The NGN quality of service mechanisms should be designed to reduce the impact of traffic burstiness on buffer management. For this reason, we propose an active dropping mechanism to deal with the effective bandwidth utilization in this paper. We use scalable video coding extension of H.264/AVC standard to provide different video quality for users of different levels. In the proposed dropping mechanism, when the network loading exceeds the threshold, the dropping mechanism starts to drop data of the enhancement layers for users of low service level. The dropping probability alters according to the change in network loading. With the dropping mechanism, the base station increases the system capability and users are able to obtain better service quality when the system is under heavy loading. We also design several methods to adjust the threshold value dynamically. By using the proposed mechanism, better quality can be provided when the network is in congestion.
The effects of the barium/titanium (Ba/Ti) ratio on the crystalline phase, Curie temperature, and dielectric properties of solid-state-reacted BaTiO3 powder were investigated. The experimental results showed that tetragonality decreased and the Curie temperature shifted to lower temperature when the Ba/Ti ratio strayed from 1.0. The BaTiO3 powder had the maximum dielectric constant when the Ba/Ti approaching 1.0.
The phase evolution, nucleation, and sintered ceramics of barium titanate (BaTiO3, BT) powder prepared by solid-state synthesis with an ultrafine starting material (27 m2/g of BaCO3 and 190 m2/g of TiO2) were investigated in this study. Surface diffusion between BaCO3 and TiO2 was observed at a relatively low temperature of 400 °C by transmission electron microscopy. Rapid nucleation of the BT and cubic BT phases was observed at 500 °C by x-ray diffraction. The derivative thermogravimetry curve clearly shows a single step of BT formation at 600 °C. In short, pure BT particles with an average particle size of 250 nm and high tetragonality were prepared by solid-state synthesis, which produced X7R ceramics with high dielectric permittivity, high insulation resistance, and a clear core–shell structure.
Disruption of cell membranes triggers rapid metabolic energy exhaustion, then acute cellular necrosis. Cell membrane dysfunction due to loss of structure integrity is the pathology of tissue death in trauma, muscular dystrophies, reperfusion injuries and common diseases. It is now established that certain PEG-based biocompatible polymers, such as Poloxamer 188, Poloxamine 1107 and PEG, are effective in sealing of injured cell membranes, and thus can prevent acute necrosis if delivered within a few hours after injury. Despite these broad applications of PEG-based polymers for human health, the fundamental mechanisms of how PEG-based polymers interact with cell membranes are still under debate. Here, the effects of PEG-based biocompatible polymers on phospholipid membrane integrity under external stimuli (osmotic stress and oxidative stress) were explored using giant unilamellar vesicles (GUVs) as model cell membranes. Through fluorescence leakage assays and time-lapse fluorescence microscopy, we directly observed that the surface-adsorbed P188 can efficiently inhibits the loss of structural integrity of giant unilamellar vesicles (GUVs) under hypo-osmotic stress. We propose that the adsorption of polymers on the membrane surface is responsible for the cell membrane resealing process, while the insertion of the hydrophobic portion of the polymers increases membrane permeability. To elucidate the mechanism by which hydrophilic polymers help restore membrane integrity while their hydrophobic counterparts disrupt it, 1H Overhauser Dynamic Nuclear Polarization (ODNP)-NMR spectroscopy, a newly developed NMR technique that provides unprecedented resolution for differentiating weak surface adsorption versus translocation of polymers to membranes, was employed to sensitively detect polymer-lipid membrane interactions through the modulation of local hydration dynamics in lipid membranes. Our study shows that P188—the most hydrophilic poloxamer known as a membrane sealant—weakly adsorbs onto the membrane surface, yet effectively retards membrane hydration dynamics. Contrarily, P181—the most hydrophobic poloxamer known as a membrane permeabilizer—initially penetrates past lipid headgroups and enhances intrabilayer water diffusivity. Consequently, our results illustrate that the relative hydrophilic/hydrophobic ratio of the polymer dictates its functions. These findings gleaned from local hydration dynamics are well supported by our thermodynamics and fluorescence data.
A conservative modification to the ghost fluid method (GFM) is developed for compressible multiphase flows. The motivation is to eliminate or reduce the conservation error of the GFM without affecting its performance. We track the conservative variables near the material interface and use this information to modify the numerical solution for an interfacing cell when the interface has passed the cell. The modification procedure can be used on the GFM with any base schemes. In this paper we use the fifth order finite difference WENO scheme for the spatial discretization and the third order TVD Runge-Kutta method for the time discretization. The level set method is used to capture the interface. Numerical experiments show that the method is at least mass and momentum conservative and is in general comparable in numerical resolution with the original GFM.
Faience production methods include efflorescence, direct glaze application, and cementation glazing. However, similar processing has been used with a variety of other materials, such as glazed monolithic quartz, ground and re-fired faience, and steatite bodies. Furthermore, faience technology has been linked by similar processing to glass, synthetic pigment and glazing technologies. Here we reinforce these cross-craft relationships by comparing the range of similar functioning chemical elements in faience and glazed artifacts from a variety of archaeological sites that range from the Indus Valley to the Mediterranean. This broad comparative method based primarily on x-ray fluorescence analysis reveals trends in faience production, relationships with metallurgical technologies, and aspects of processing that provide areas of study that may be considered more closely in the future.
Commission 33 held its business session in the afternoon of Friday 7 August 2009. The president briefly described developments during the previous months. A short discussion followed about the activities of the Commission and whether it should play a more active role in view of the many on-going surveys relevant to the subject of the Galaxy.