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The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain incompletely understood. Here we examined how LSD affects probabilistic reversal learning (PRL) in healthy humans.
Healthy volunteers received intravenous LSD (75 μg in 10 mL saline) or placebo (10 mL saline) in a within-subjects design and completed a PRL task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning (RL) were fitted to the behavioural data to assess how LSD affected the updating (‘learning rates’) and deployment of value representations (‘reinforcement sensitivity’) during choice, as well as ‘stimulus stickiness’ (choice repetition irrespective of reinforcement history).
Raw data measures assessing sensitivity to immediate feedback (‘win-stay’ and ‘lose-shift’ probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was the enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploration. Reinforcement sensitivity differed by phase.
Increased RL rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.
Patent data have been utilized for engineering design research for long because it contains massive amount of design information. Recent advances in artificial intelligence and data science present unprecedented opportunities to mine, analyse and make sense of patent data to develop design theory and methodology. Herein, we survey the patent-for-design literature by their contributions to design theories, methods, tools, and strategies, as well as different forms of patent data and various methods. Our review sheds light on promising future research directions for the field.
Novel concepts are essential for design innovation and can be generated with the aid of data stimuli and computers. However, current generative design algorithms focus on diagrammatic or spatial concepts that are either too abstract to understand or too detailed for early phase design exploration. This paper explores the uses of generative pre-trained transformers (GPT) for natural language design concept generation. Our experiments involve the use of GPT-2 and GPT-3 for different creative reasonings in design tasks. Both show reasonably good performance for verbal design concept generation.
Children’s peer victimization trajectories and their longitudinal associations with externalizing and internalizing problems were investigated from Grades 2 to 5. Secondary data analysis was performed with the Early Childhood Longitudinal Study (ECLS-K-2011; n = 13,860, Mage = 8.1 years old in the spring of Grade 2; 51.1% male, 46.7% White, 13.2% African-American, 25.3% Hispanic or Latino, 8.5% Asian, and 6.1% other or biracial). Children who experienced high and persistent levels of peer victimization (high-chronic victims) exhibited co-occurring externalizing and internalizing problems. Moreover, among high-chronic victims, boys had a more pronounced increase in their externalizing trajectories, and girls had greater increases in their social anxiety trajectories. In contrast, those with decreasing peer victimization across time exhibited signs of recovery, particularly with respect to their social anxiety. These findings elucidated how chronic, increasing, and decreasing victims exhibited distinct patterns in the co-occurring development of their externalizing and internalizing problems, and how findings varied depending on the form of problem behavior and by child sex.
Without rapid international action to curb greenhouse gas emissions, climate scientists have predicted catastrophic sea-level rise by 2100. Globally, archaeologists are documenting the effects of sea-level rise on coastal cultural heritage. Here, the authors model the impact of 1m, 2m and 5m sea-level rise on China's coastal archaeological sites using data from the Atlas of Chinese Cultural Relics and Shanghai City's Third National Survey of Cultural Relics. Although the resulting number of endangered sites is large, the authors argue that these represent only a fraction of those actually at risk, and they issue a call to mitigate the direct and indirect effects of rising sea levels.
To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression.
In the present study, we examined 79 patients (57 males; age range = 17–70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31].
Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation.
These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.
The current study used behavioural and electroencephalograph measures to compare the transferability of three home-based interventions — cognitive training (CT), neurofeedback training (NFT), and CT combined with NFT — for reducing symptoms in children with attention-deficit/hyperactivity disorder (AD/HD). Following a multiple-baseline single-case experimental design, twelve children were randomised to a training condition. Each child completed a baseline phase, followed by an intervention phase. The intervention phase consisted of 20 sessions of at-home training. Tau-U analysis and standardised visual analysis were adopted to detect effects. Results showed that CT improved inhibitory function and NFT improved alpha EEG activity and working memory. The combined condition, which was a reduced ‘dose’ of CT and NFT, did not show any improvements. The three conditions did not alleviate AD/HD symptoms. While CT and NFT may have transfer effects on executive functions, considering the lack of improvement in symptoms, this study does not support CT and NFT on their own as a treatment for children with AD/HD.
Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
The function and change of global soil carbon (C) reserves in natural ecosystems are key regulators of future carbon-climate coupling. Microbes play a critical role in soil carbon cycling and yet there is poor understanding of their roles and C metabolism flexibility in many ecosystems. We wanted to determine whether vegetation type and climate zone influence soil microbial community composition (fungi and bacteria) and carbon resource preference. We used a biomarker (phospholipid fatty acids, PLFAs), natural abundance 13C and 14C probing approach to measure soil microbial composition and C resource use, along a 1900–4167-m elevation gradient on Mount Gongga (7556 m asl), China. Mount Gongga has a vertical mean annual temperature gradient of 1.2–10.1°C and a diversity of typical vegetation zones in the Tibetan Plateau. Soils were sampled at 10 locations along the gradient capturing distinct vegetation types and climate zones from lowland subtropical-forest to alpine-meadow. PLFA results showed that microbial communities were composed of 2.1–51.7% bacteria and 2.0–23.2% fungi across the elevation gradient. Microbial biomass was higher and the ratio of soil fungi to bacteria (F/B) was lower in forest soils compared to meadow soils. δ13C varied between −33‰ to −17‰ with C3 plant carbon sources dominant across the gradient. Soil organic carbon (SOC) turnover did not vary among three soils we measured from three forest types (i.e., evergreen broadleaved subtropical, mixed temperate, coniferous alpine) and dissolved organic carbon (DOC) turnover decreased with soil elevation. Forest soil microbial PLFA 14C and δ13C measurements showed that forest type and climate were related to different microbial C use. The 14C values of microbial PLFAs i15, a15, 16:1, br17 decreased with elevation while those of C16:0, cyC17, and cyC19 did not show much difference among three forest ecosystems. Bacteria and bacillus represented by C16:1 and brC17 showed considerable microbial C metabolism flexibility and tended to use ancient carbon at higher altitudes. Anaerobes represented by cyC17 and cyC19 showed stronger C metabolism selectivity. Our findings reveal specific C source differences between and within soil microbial groups along elevation gradients.
During the last few decades, bed-elevation profiles from radar sounders have been used to quantify bed roughness. Various methods have been employed, such as the ‘two-parameter’ technique that considers vertical and slope irregularities in topography, but they struggle to incorporate roughness at multiple spatial scales leading to a breakdown in their depiction of bed roughness where the relief is most complex. In this article, we describe a new algorithm, analogous to wavelet transformations, to quantify the bed roughness at multiple scales. The ‘Self-Adaptive Two-Parameter’ system calculates the roughness of a bed profile using a frequency-domain method, allowing the extraction of three characteristic factors: (1) slope, (2) skewness and (3) coefficient of variation. The multi-scale roughness is derived by weighted-summing of these frequency-related factors. We use idealized bed elevations to initially validate the algorithm, and then actual bed-elevation data are used to compare the new roughness index with other methods. We show the new technique is an effective tool for quantifying bed roughness from radar data, paving the way for improved continental-wide depictions of bed roughness and incorporation of this information into ice flow models.
Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose–response effects. This meta-analysis aimed to find the dose–response relationship between alcohol, coffee or tea consumption and cognitive deficits.
Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose–response relationship graphs.
The search identified 29 prospective studies from America, Japan, China and some European countries. The dose–response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92–0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits.
Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.
The association between gray matter and cognitive dysfunction in young major depression remains unclear.
To investigate the brain gray matter and the correlation with cognitive function in first-episode, treatment-naive patients with major depressive disorder (MDD).
To explore brain structural pathological mechanisms of cognitive impairment in MDD.
46 MDD aged 18-45 year and 46 controls were assessed by Wisconsin Card Sorting Test (WCST) and Trail making test (TMT). Then, 30 patients and 30 controls were obtained by MRI scan.
The total number of errors, number of preservative errors, random errors of WSCT in MDD were significantly more than that in controls, and the completion time in the TMT-A and TMT-B was longer than that in controls. MDD showed significant less gray matter volumns than controls in frontal lobe (right precentral gyrus, bilateral superior frontal gyrus and right middle frontal gyrus), parietal lobe (left postcentral gyrus, left paracentral lobule, and bilateral precuneus), temporal lobe (right superior temporal gyrus), and occipital lobe (left superior occipital gyrus). There was a significant negative correlation between left postcentral gyrus and left superior occipital gyrus gray matter density and the TMT-B completion time (r=-0.462, P=0.017; r=-0.448, P=0.022).
The first-episode MDD patient exhibiteded cognitive impairment and showed significant lower gray matter density than controls in frontal lobe, parietal lobe, temporal lobe, occipital lobe. Decreased gray matter density in left postcentral gyrus and left superior occipital gyrus may be involved in the executive dysfunction.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
Chinese men who have sex with men (MSM) are at high risk for depression, anxiety and suicide. The estimated prevalence of these problems is essential to guide public health policy, but published results vary. This meta-analysis aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and suicide among Chinese MSM.
Systematic searches of EMBASE, MEDLINE, PsycINFO, PubMed, CNKI and Wanfang databases with languages restricted to Chinese and English for studies published before 10 September 2019 on the prevalence of depressive symptoms, anxiety symptoms, suicidal ideation, suicide plans and suicide attempts among Chinese MSM. Studies that were published in the peer-reviewed journals and used validated instruments to assess depression and anxiety were included. The characteristics of studies and the prevalence of depression and anxiety symptoms, suicidal ideation, suicide plans and suicide attempts were independently extracted by authors. Random-effects modelling was used to estimate the pooled rates. Subgroup analysis and univariate meta-regression were conducted to explore potential sources of heterogeneity. This study followed the PRISMA and MOOSE.
Sixty-seven studies were included. Fifty-two studies reported the prevalence of depressive symptoms, with a combined sample of 37 376 people, of whom 12 887 [43.2%; 95% confidence interval (CI), 38.9–47.5] reported depressive symptoms. Twenty-seven studies reported the prevalence of anxiety symptoms, with a combined sample of 10 531 people, of whom 3187 (32.2%; 95% CI, 28.3–36.6) reported anxiety symptoms. Twenty-three studies reported the prevalence of suicidal ideation, with a combined sample of 15 034 people, of whom 3416 (21.2%; 95% CI, 18.3–24.5) had suicidal ideation. Nine studies reported the prevalence of suicide plans, with a combined sample of 5271 people, of whom 401 (6.2%; 95% CI, 3.9–8.6) had suicide plans. Finally, 19 studies reported the prevalence of suicide attempts, with a combined sample of 27 936 people, of whom 1829 (7.3%; 95% CI, 5.6–9.0) had attempted suicide.
The mental health of Chinese MSM is poor compared with the general population. Efforts are warranted to develop interventions to prevent and alleviate mental health problems among this vulnerable population.
We return to the long-standing question ‘Who owns the assets in a defined benefit pension plan?’ Unlike earlier studies, we condition the market's assessment of implicit property rights on the sponsoring firm's financial health. Valuations of financially strong firms, and those that are strengthening, are more responsive to pension plan funding. For these firms, each extra dollar of net plan assets is valued at between $0.50 and $1.00. In contrast, for weak and weakening firms, valuation effects are statistically indistinguishable from zero. This result is consistent with the higher likelihood that they will renege on their pension obligations.
Resistant starch (RS) was recently approved to exert a powerful influence on gut health, but the effect of RS on the caecal barrier function in meat ducks has not been well defined. Thus, the effect of raw potato starch (RPS), a widely adopted RS material, on microbial composition and barrier function of caecum for meat ducks was determined. A total of 360 Cherry Valley male ducks of 1-d-old were randomly divided and fed diets with 0 (control), 12, or 24 % RPS for 35 d. Diets supplemented with RPS significantly elevated villus height and villus height:crypt depth ratio in the caecum. The 16S rRNA sequence analysis indicated that the diet with 12 % RPS had a higher relative abundance of Firmicutes and the butyrate-producing bacteria Faecalibacterium, Subdoligranulum, and Erysipelatoclostridium were enriched in all diets. Lactobacillus and Bifidobacterium were significantly increased in the 24 % RPS diet v. the control diet. When compared with the control diet, the diet with 12 % RPS was also found to notably increase acetate, propionate and butyrate contents and up-regulated barrier-related genes including claudin-1, zonula occludens-1, mucin-2 and proglucagon in the caecum. Furthermore, the addition of 12 % RPS significantly reduced plasma TNF-α, IL-1β and endotoxin concentrations. These data revealed that diets supplemented with 12 % RPS partially improved caecal barrier function in meat ducks by enhancing intestinal morphology and barrier markers expression, modulating the microbiota composition and attenuating inflammatory markers.
In this study, the thermal deformation of a machine tool structure due to the heat generated during operation was analyzed, and embedded cooling channels were applied to exchange the heat generated during the operation to achieve thermal error suppression. Then, the finite volume method was used to simulate the effect of cooling oil temperature on thermal deformation, and the effect of thermal suppression was experimentally studied using a feed system combined with a cooler to improve the positioning accuracy of the machine tool. In this study, the supply oil temperature in the structural cooling channels was found to significantly affect the position accuracy of the moving table and moving carrier. If the supply oil temperature in the cooling channels is consistent with the operational ambient temperature, the position accuracy of the moving table in the Y direction and the moving carrier in the X and Z directions has the best performance under different feed rates. From the thermal suppression experiments of the embedded cooling channels, the positioning accuracy of the feed system can be improved by approximately 25.5 % during the dynamic feeding process. Furthermore, when the hydrostatic guideway is cooled and dynamic feeding is conducted, positioning accuracy can be improved by up to 47.8 %. The machining accuracy can be improved by approximately 60 % on average by using the embedded cooling channels in this study. Therefore, thermal suppression by the cooling channels in this study can not only effectively improve the positioning accuracy but also enhance machining accuracy, proving that the method is effective for enhancing machine tool accuracy.
Rumen-protected betaine (RPB) can enhance betaine absorption in the small intestine of ruminants, while betaine can alter fat distribution and has the potential to affect the meat quality of livestock. Hence, we hypothesized that RPB might also affect the meat quality of lambs. Sixty male Hu sheep of similar weight (30.47 ± 2.04 kg) were selected and randomly subjected to five different treatments. The sheep were fed a control diet (control treatment, CTL); 1.1 g/day unprotected-betaine supplemented diet (UPB); or doses of 1.1 g/day (low RPB treatment; L-PB), 2.2 g/day (middle RPB treatment; M-PB) or 3.3 g/day (high RPB treatment; H-PB) RPB-supplemented diet for 70 days. Slaughter performance, meat quality, fatty acid and amino acid content in the longissimus dorsi (LD) muscle, shoulder muscle (SM) and gluteus muscle (GM) were measured. Compared with CTL, betaine (including UPB and RPB) supplementation increased the average daily weight gain (ADG) (P < 0.05) and average daily feed intake (P < 0.01) of lambs. Rumen-protected betaine increased ADG (P < 0.05) compared with UPB. With increasing RPB doses, the eye muscle area of the lambs linearly increased (P < 0.05). Compared with CTL, betaine supplementation decreased water loss (P < 0.05) in SM and increased pH24 in the SM (P < 0.05) and GM (P < 0.05). Compared with UPB, RPB decreased water loss in the GM (P < 0.01), decreased shear force (P < 0.05) in the LD and SM and increased the pH of the meat 24 h after slaughter (pH24). With increasing RPB doses, the shear force and b* value in the LD linearly decreased (P < 0.05), and the pH24 of the meat quadratically increased (P < 0.05). Compared with CTL, betaine supplementation increased the polyunsaturated fatty acid in the GM (P < 0.05). Compared with UPB, RPB supplementation decreased the saturated fatty acid (SFA) content in the LD (P < 0.05) and increased the unsaturated fatty acids (UFA), mono-unsaturated fatty acids and UFA/SFA ratio in the LD (P < 0.05). Compared with CTL, the content of histidine in the LD increased with betaine supplementation. Compared with UPB, RPB supplementation increased the content of total free amino acids and flavor amino acids in the LD of lambs (P < 0.05). With increasing RPB, the isoleucine and phenylalanine contents in the LD linearly increased (P < 0.05). Overall, the data collected indicated that the meat quality of lambs (especially in the LD) improved as a result of betaine supplementation, and RPB showed better effects than those of UPB.