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Individuals with intellectual and developmental disability (IDD) can have a high prevalence of pain, which can be managed with prescription opioids. However, the prevalence of substance use disorder is also high in this population, raising concern about opioid-related adverse events.
To assess the risk of opioid-related adverse events following opioid initiation among adults with versus without IDD.
We conducted a population-based, propensity score matched cohort study on all adults starting prescription opioid therapy in Ontario, Canada, between January 2013 and December 2018. The outcomes of interest were opioid toxicity, new opioid use disorder (OUD) diagnosis and dose escalation (≥90 mg morphine or equivalent) in the year after opioid initiation. We used Cox proportional hazards models to assess the association between IDD diagnosis and each outcome.
The hazards of opioid toxicity and OUD were significantly higher in those with IDD compared with those without IDD in unmatched analyses (opioid toxicity hazard ratio 3.19, 95% CI 2.81–5.18; OUD hazard ratio 2.36, 95% CI 2.10–2.65), whereas the hazard of dose escalation was significantly lower (hazard ratio 0.76, 95% CI 0.66–0.88). Findings were no longer significant in propensity score matched models for opioid toxicity and dose escalation, whereas the hazard of OUD diagnosis was attenuated substantially in those with IDD (hazard ratio 0.79, 95% CI 0.68–0.91).
IDD diagnosis is not a driver of opioid-related harm. The increased risk we observed is likely driven by various risk factors often present in this population.
There are various matrices to represent parallel mechanisms. It is essential to design a kind of approach to not only denote the parallel structures but also disclose the joint directions. In this paper, a novel methodology called the kinematic joint matrix (KJM) is proposed. It possesses the mapping relations with parallel manipulators with three kinds of kinematic joints. The size of such matrix is smaller when compared with that of topology matrix. A series of two to six degrees-of-freedom parallel architectures is denoted by the KJM. A convenient approach using a special block diagram is introduced to distinguish various kinds of kinematic joint matrices. In addition, detailed comparisons between KJM and topology matrix are investigated. Three regulations are proposed for the latter to be applicable to parallel mechanisms.
In this paper, we study the Friedrichs extensions of Sturm–Liouville operators with complex coefficients according to the classification of B. M. Brown et al. . We characterize the Friedrichs extensions both by boundary conditions at regular endpoint and asymptotic behaviours of elements in the maximal operator domains at singular endpoint. Some of spectral properties are also involved.
Instrument delivery is critical part in vascular intervention surgery. Due to the soft-body structure of instruments, the relationship between manipulation commands and instrument motion is non-linear, making instrument delivery challenging and time-consuming. Reinforcement learning has the potential to learn manipulation skills and automate instrument delivery with enhanced success rates and reduced workload of physicians. However, due to the sample inefficiency when using high-dimensional images, existing reinforcement learning algorithms are limited on realistic vascular robotic systems. To alleviate this problem, this paper proposes discrete soft actor-critic with auto-encoder (DSAC-AE) that augments SAC-discrete with an auxiliary reconstruction task. The algorithm is applied with distributed sample collection and parameter update in a robot-assisted preclinical environment. Experimental results indicate that guidewire delivery can be automatically implemented after 50k sampling steps in less than 15 h, demonstrating the proposed algorithm has the great potential to learn manipulation skill for vascular robotic systems.
Adherence to healthy lifestyles can be beneficial for depression among adults, but the intergenerational impact of maternal healthy lifestyles on offspring depressive symptoms is unknown.
In total, 10 368 mothers in Nurses' Health Study II and 13 478 offspring in the Growing Up Today Study were paired. Maternal and offspring healthy lifestyles were defined as a composite score including a healthy diet, normal body mass index (BMI), never-smoking, light-to-moderate consumption of alcohol, and regular moderate-to-vigorous physical activity. Maternal lifestyles were assessed during their offspring's childhood. Offspring depressive symptoms were repeatedly assessed five times using the Center for Epidemiological Studies Depression Scale-10 (CESD-10); the offspring were between the ages of 14 and 30 when the first CESD-10 was assessed. Covariates included maternal variables (age at baseline, race/ethnicity, antidepressant use, pregnancy complications, etc.) and offspring age and sex.
Children of mothers with the healthiest lifestyle had significantly fewer depressive symptoms (a 0.30 lower CESD-10 score, 95% confidence interval (CI) 0.09–0.50) in comparison with children of mothers with the least healthy lifestyle. The association was only found significant in female offspring but not in males. For individual maternal lifestyle factors, a normal BMI, never-smoking, and adherence to regular physical activity were independently associated with fewer depressive symptoms among the offspring. The association between maternal healthy lifestyles and offspring depressive symptoms was mediated by offspring's healthy lifestyles (mediation effect: 53.2%, 95% CI 15.8–87.3).
Our finding indicates the potential mechanism of intergenerational transmission of healthy lifestyles to reduce the risk of depressive symptoms in offspring.
The popularity of the online social media in China promotes a dynamic digital drive for both global and glocalised communications, facilitating the emergence of more connected intercultural language practices unimaginable in the past. Social media also creates a vast community where pervasive translanguaging practices take place daily. Translanguaging hybrids coined by Chinese university students on WeChat are exactly a case in point. WeChat is a free platform launched in 2011 by Tencent. Well established in China and the world over, Tencent provides multimodal instant messaging services. Open to world cultures, these students show ingenuity in translanguaging linguistic play in their daily text messages; meanwhile, their creative coinage of translanguaging hybrids influences the entire WeChat community. Written language in the WeChat community, often amounting to a new form of speech, deserves serious scholarly inquiry.
High-molecular-weight glutenin subunits (HMW-GS) contribute to dough elasticity and bread baking quality in wheat. In this study, wheat varieties were classified based on their HMW-GS composition into three groups: 1Dx5 (5 + 10, Gaoyou 8901, Xinmai 28, Xinmai 19, Xinmai 26 and Jinbaoyin), 1Dx2 (2 + 12, Zhoumai 24, Xinmai 9 and Yumai) and 1Dx4 (4 + 12, Aikang 58). Sequence analysis showed that 1Dx-GY8901, 1Dx-XM28, 1Dx-XM19 and 1Dx-XM26 were similar to the 1Dx5 gene and clustered on the same branch, while 1Dx-AK58, 1Dx-ZM24, 1Dx-JBY, 1Dx-YM, 1Dx-XM9 and 1Dx-JBY were more similar to the 1Dx2 gene and clustered on the same branch with 1Dx.2.2. There was a mutation of Ser to Cys at position S2, for an extra Cys in the repeat regions of 1Dx-XM19, 1Dx-XM26, 1Dx-XM28 and 1Dx-GY8901. The wheat HMW-GS genes exhibited similar percentages of α-helix, extended strand, β-turn and random coil structure, with ranges of 13.33–13.59, 4.77–5.78, 7.08–9.18 and 72.3–73.94%, respectively. Sequence conservation and the composition of HMW-GS subunits were also analysed for a series of strong gluten wheat varieties, Xinmai 9 (1, 7 + 8, 2 + 12), Xinmai 19 (1, 7 + 9, 5 + 10), Xinmai 26 (1, 7 + 8, 5 + 10) and Xinmai 28 (1, 7 + 9, 5 + 10). The results of this work should facilitate future breeding efforts and provide the theoretical basis for wheat quality improvement.
To identify risk factors for mortality in intensive care units (ICUs) in Asia.
Prospective cohort study.
The study included 317 ICUs of 96 hospitals in 44 cities in 9 countries of Asia: China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam.
Patients aged >18 years admitted to ICUs.
In total, 157,667 patients were followed during 957,517 patient days, and 8,157 HAIs occurred. In multiple logistic regression, the following variables were associated with an increased mortality risk: central-line–associated bloodstream infection (CLABSI; aOR, 2.36; P < .0001), ventilator-associated event (VAE; aOR, 1.51; P < .0001), catheter-associated urinary tract infection (CAUTI; aOR, 1.04; P < .0001), and female sex (aOR, 1.06; P < .0001). Older age increased mortality risk by 1% per year (aOR, 1.01; P < .0001). Length of stay (LOS) increased mortality risk by 1% per bed day (aOR, 1.01; P < .0001). Central-line days increased mortality risk by 2% per central-line day (aOR, 1.02; P < .0001). Urinary catheter days increased mortality risk by 4% per urinary catheter day (aOR, 1.04; P < .0001). The highest mortality risks were associated with mechanical ventilation utilization ratio (aOR, 12.48; P < .0001), upper middle-income country (aOR, 1.09; P = .033), surgical hospitalization (aOR, 2.17; P < .0001), pediatric oncology ICU (aOR, 9.90; P < .0001), and adult oncology ICU (aOR, 4.52; P < .0001). Patients at university hospitals had the lowest mortality risk (aOR, 0.61; P < .0001).
Some variables associated with an increased mortality risk are unlikely to change, such as age, sex, national economy, hospitalization type, and ICU type. Some other variables can be modified, such as LOS, central-line use, urinary catheter use, and mechanical ventilation as well as and acquisition of CLABSI, VAE, or CAUTI. To reduce mortality risk, we shall focus on strategies to reduce LOS; strategies to reduce central-line, urinary catheter, and mechanical ventilation use; and HAI prevention recommendations.
This study aimed to analyze the clinical effects of microdissection testicular sperm extraction (micro-TESE) surgery combined with an intracytoplasmic sperm injection (ICSI) regimen in the treatment of non-obstructive azoospermia (NOA) patients with different etiologies. In total, 128 NOA patients participated in this study, in which they received infertility treatment by micro-TESE surgery combined with an ICSI regimen, and all patients were divided into three groups [the Klinefelter syndrome (KS), the idiopathic and the secondary NOA groups]. In addition, the sperm retrieval rate (SRR), fertilization rate, embryo development status and clinical treatment effects were analyzed. Among the 128 NOA patients, the SRR of KS NOA patients was 48.65%, those of idiopathic and the secondary patients were 33.82% and 73.91%, respectively. Regardless of etiologies, there was no correlation with age, hormone value or testicular volume. Further analysis showed that the SRR of the KS group was positively related with testosterone (T) values, and the SRR of the secondary group had a positive relationship with follicle-stimulating hormone or luteinizing hormone values. In the subsequent clinical treatment, the retrieved sperm was subjected to ICSI and achieved good treatment effects, especially in the secondary group, and the implantation rate (55.56%) and clinical pregnancy rate (68.42%) were both higher than those of the idiopathic group (28.75% and 40.00%) and KS group (22.05% and 30.77%). Micro-TESE surgery combined with ICSI insemination is the most effective treatment regimen for NOA patients. The SRR of NOA patients with different etiologies are related to certain specific factors, and micro-TESE surgery seems to be the ideal and only way to have biological children.
Telocyte (TC)—a new type of interstitial cell with long telopodes, can form cellular junctions with various tissues or cells to participate in the regulation of multitudes of physiological activities and diseases. This study aimed to characterize the morphology, molecular features, and potential functions of hormone regulation in Chinese soft-shelled turtle (Pelodiscus sinensis) testis TCs at different reproductive stages by histological evaluation, immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy. During hibernation, TCs were widely distributed in the interstitial tissue. In contrast, during reproductive activity, TCs were noted to be in close proximity with peritubular myoid cells surrounding the seminiferous tubule. Moreover, formed cell–cell junctions were observed between TCs and PTMs. The results of IHC and IF showed that the immunophenotype of testicular TCs in hibernating Chinese soft-shelled turtles is CD34+Vimentin−, while the reproductive telopodes (Tps) show low expression of vimentin. The androgen receptor is expressed in Tps of TCs of testis during hibernation. Our results showed also that TCs in seasonal breeding animals regulate the activity of neighboring cells by releasing extracellular microvesicles (EXMVs), thus influencing the activity of spermatogenesis and steroidogenesis. Consideration of our novel and interesting results indicate that the whole area warrants further research.
The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association.
From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45–64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively.
In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46–2.00) for depression at any age, 1.72 (1.36–2.17) for early-life, 1.51 (1.19–1.90) for midlife, and 4.10 (2.02–8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09).
Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid vs. solid), and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15,538 participants, free of NAFLD, other liver diseases, cardiovascular disease, cancer, or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item food frequency questionnaire. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for NAFLD risk with added sugar intake. During a median follow-up of 4.2 years, 3,476 incident NAFLD cases were documented. After adjusting for age, sex, body mass index and its change from baseline to follow-up, lifestyle factors, personal and family medical history, and overall diet quality, the multivariable HRs (95% CIs) of NAFLD risk were 1.18 (1.06, 1.32) for total added sugars, 1.20 (1.08, 1.33) for liquid added sugars, and 0.96 (0.86, 1.07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
This study presents zircon U–Pb geochronology and Hf and O isotope data for granitic rocks in the Zijinshan ore field, southwestern Fujian Province, China. The intrusive rocks comprise monzogranite, granite and granodiorite. The magmatic zircon U–Pb ages from these granitic rocks can be divided into four episodes: episodes 1 (157.9–159.9 Ma) and 2 (141 Ma) in the Late Jurassic and episodes 3 (108.1–103.2 Ma) and 4 (97.5–99.7 Ma) in the Middle and Late Cretaceous, respectively. Patterns of rare-earth elements (REE) show enrichment in light REE and obvious negative Eu anomalies. These rocks are also enriched in Rb, Th, U, La, Ce, Nd and Hf, and depleted in Ba, Nb, Sr, P and Ti. The increasing La/Yb ratio and decreasing heavy REE content with decreasing age may imply an increasing contribution of mantle-derived materials from the Late Jurassic to Cretaceous. The zircon ϵHf(t) and δ18O values, ranging from −37.7 to −2.8 and 12.0 ‰ to 6.3 ‰, respectively, indicate that the lower crust is an important source of granitic rocks. There was a significant increase in ϵHf(t) values and a decrease in δ18O values in the younger magmatic episodes (3 and 4), which ranged from −11.4 to −0.6 and 10.7 to 6.3 ‰, respectively. This suggests an increasing contribution of mantle-derived magma to the crustal melts from the Late Jurassic to late Early Cretaceous in response to the changing regional tectonic setting from compression to extension and an increasing interaction between the crust and mantle.
In this study, basing on the level-set and point-particle methods, we have developed a numerical methodology for simulating the dynamics of colloidal droplets under flow conditions in which the particle–particle, particle–interface and particle–fluid interactions are all taken into account efficiently. By using this methodology, we have determined the essential role of particle-laden interfaces in the deformation of colloidal droplets in simple shear flow with relatively low particle concentrations. Generally, adsorbed particles strongly enhance the deformability of the whole droplet, which is principally attributed to the particle-induced reduction of the effective surface tension. Systematic simulations are performed to reveal the detailed roles of interparticle interactions and particle surface coverage in the deformation of particle-covered droplets. Most importantly, we find the promotion effect of adsorbed particles on the droplet deformation cannot be completely included via the effective capillary number characterizing the particle-induced overall reduction of the effective surface tension, which is particularly obvious at high particle coverage. We propose two potential reasons for this surprising phenomenon, i.e. the convection-induced non-uniform distribution of adsorbed particles over the droplet surface and the particle-induced reduction of the droplet surface mobility, which have not been discussed yet in previous numerical and experimental studies of particle-covered droplets in shear flow.
Numerous studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed differences in specific brain regions of patients with bipolar disorder (BD), but the results have been inconsistent.
A whole-brain voxel-wise meta-analysis was conducted on resting-state functional imaging and VBM studies that compared differences between patients with BD and healthy controls using Seed-based d Mapping with Permutation of Subject Images software.
A systematic literature search identified 51 functional imaging studies (1842 BD and 2190 controls) and 83 VBM studies (2790 BD and 3690 controls). Overall, patients with BD displayed increased resting-state functional activity in the left middle frontal gyrus, right inferior frontal gyrus (IFG) extending to the right insula, right superior frontal gyrus and bilateral striatum, as well as decreased resting-state functional activity in the left middle temporal gyrus extending to the left superior temporal gyrus and post-central gyrus, left cerebellum, and bilateral precuneus. The meta-analysis of VBM showed that patients with BD displayed decreased VBM in the right IFG extending to the right insula, temporal pole and superior temporal gyrus, left superior temporal gyrus extending to the left insula, temporal pole, and IFG, anterior cingulate cortex, left superior frontal gyrus (medial prefrontal cortex), left thalamus, and right fusiform gyrus.
The multimodal meta-analyses suggested that BD showed similar patterns of aberrant brain activity and structure in the insula extending to the temporal cortex, fronto-striatal-thalamic, and default-mode network regions, which provide useful insights for understanding the underlying pathophysiology of BD.
Copy number variation (CNV) is a very common type of gene variation with high frequency. In recent years, CNV has been paid more attention in various fields, especially in livestock and poultry breeding, which has promoted the progress of breeding. WW domain binding protein 1-like (WBP1L) is a protein coding gene, which plays an important role in cattle populations, and its function has been extensively studied, but it is not clear whether the copy number of the gene can affect the growth and development of cattle populations. In this study, CNV of WBP1L gene was detected in 732 cattle of seven breeds (Qinchuan cattle, QC; Pinan cattle, PN; Yuengling cattle, YL; Xianan cattle, XN; Jiaxian cattle, JX; natural Guyuan cattle, NGY; Jian cattle, JA). In addition, the relationship between CNV and growth phenotype of cattle was studied. The experimental data indicate that the copy number of WBP1L was obviously correlated with heart girth of PN cattle (**P < 0.01), rump length (RL) and body weight (BW) of PN cattle (*P < 0.05), withers height (WH), RL, body length, chest depth and BW of JX cattle (*P < 0.05), WH of NGY cattle (*P < 0.05) and WH of JA cattle (*P < 0.05). It was proved that CNV of WBP1L gene could be used as molecular marker locus for genetic breeding of the above four cattle breeds.
Dietary patterns (DP) rich in plant foods are associated with improved health and reduced non-communicable disease risk. In October 2021, the Nutrition Society hosted a member-led conference, held online over 2 half days, exploring the latest research findings examining plant-rich DP and health. The aim of the present paper is to summarise the content of the conference and synopses of the individual speaker presentations are included. Topics included epidemiological analysis of plant-rich DP and health outcomes, the effects of dietary interventions which have increased fruit and vegetable (FV) intake on a range of health outcomes, how adherence to plant-rich DP is assessed, the use of biomarkers to assess FV intake and a consideration of how modifying behaviour towards increased FV intake could impact environmental outcomes, planetary health and food systems. In conclusion, although there are still considerable uncertainties which require further research, which were considered as part of the conference and are summarised in this review, adopting a plant-rich DP at a population level could have a considerable impact on diet and health outcomes, as well as planetary health.
A quasi-dynamic subgrid-scale (SGS) kinetic energy one-equation eddy-viscosity model is introduced in this paper for large-eddy simulation (LES) of compressible flows. With the additional SGS kinetic energy equation, the SGS kinetic energy can be predicted properly. Then, using the dual constraints of SGS kinetic energy and the SGS kinetic energy flux, the eddy-viscosity model can be determined exactly. Taking a similar scheme as the expansion of the SGS stress, other unclosed quantities in the equations to be solved could be well modelled separately. Therefore, with the advance of the equations, all the model coefficients can be determined dynamically. Differing from the classic dynamic procedure, the new methodology needs no test filtering, and thus it could also be called a quasi-dynamic procedure. Using direct numerical simulation of compressible turbulent channel flow, the $a$$priori$ test shows that the key modelled quantities of the suggested model display high correlations with the real values. In LES of compressible turbulent channel flows of the Mach number being $1.5$ and 3.0, the proposed model can precisely predict some important quantities, including the mean velocity, Reynolds stress and turbulent flux, and it can also supply more abundant turbulent structures. For the compressible flat-plate boundary layer, the new model can correctly predict the transition process, mean velocity and turbulence intensities in the turbulent region. The results show that the proposed model has the advantage of scale adaptivity. Finally, the new model is applied to LES of turbulent mixing in spherical converging Richtmyer–Meshkov instability, and the accurate results show that the new model has a good ability for LES of complex fluids.