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OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p < 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p < 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p > 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.
We review the scholarly contributions that utilise natural language processing (NLP) techniques to support the design process. Using a heuristic approach, we gathered 223 articles that are published in 32 journals within the period 1991–present. We present state-of-the-art NLP in-and-for design research by reviewing these articles according to the type of natural language text sources: internal reports, design concepts, discourse transcripts, technical publications, consumer opinions and others. Upon summarising and identifying the gaps in these contributions, we utilise an existing design innovation framework to identify the applications that are currently being supported by NLP. We then propose a few methodological and theoretical directions for future NLP in-and-for design research.
One of the most perplexing and characteristic symptoms of the schizophrenia (SZ) patients is hallucination. The occurrence of hallucinations to be associated with altered activity in the auditory and visual cortex but is not well understood from the brain functional network dynamics in SZ.
To explore the brain abnormal basis of hallucinations in SZ with the dynamic functional connectivity (dFC).
Using magnetic resonance imaging for 83 SZ patients and 83 matched healthy controls and independent component analysis, 52 independent components (ICs) were identified as nodes and assigned into eight intrinsic connectivity networks (Figure 1A). Subsequently, we established dFC matrices and clustered them into four discrete states (Figure 1B) and three state transition metrics were obtained. To further explore the changes in the centrality of each component, eigenvector centrality (EC) was calculated and its time-varying was evaluated.
Compared to controls with FDR correction, we found that patients had more mean dwell times and fractional time in state 1 (P=0.0081 and P=0.0018), mainly with hypoconnectivity between auditory and visual network and other networks and hyperconnectivity between language and default-mode network (DMN). While, patients had less dwell times and fractional time in state 3 (P=0.0018 and P=0.0009), and decreased FC between visual network and executive control network (ECN) and increased FC between ECN and DMN than controls (Figure 2).
EC statistics showed that SZs displayed increased temporal dynamics in visual-related regions (Figure 3).
SZ was mainly manifested as altered dFC and temporal variability of nodal centrality in auditory and visual networks.
Though schizophrenia (SZ) and obsessive-compulsive disorder (OCD) are conceptualized as distinct clinical entities, they do have notable symptom overlap and a tight association. Graph-theoretical analysis of the brain connectome provides more indicators to describe the functional organization of the brain, which may help us understand the shared and disorder-specific neural basis of the two disorders.
To explore the static and dynamic topological organization of OCD and SZ as well as the relationship between topological metrics and clinical variables.
Resting state functional magnetic resonance imaging data of 31 OCD patients, 49 SZ patients, and 45 healthy controls (HC) were involved in this study (Table 1). Using independent component analysis to obtain independent components (ICs) (Figure 1), which were defined as nodes for static and dynamic topological analysis.
Static analysis showed the global efficiency of SZ was higher than HC. For nodal degree centrality, OCD exhibited decreased degree centrality in IC59 (located in visiual network) (P = 0.03) and increased degree centrality in IC38 (located in salience network) (P = 0.002) compared with HC. Dynamic analysis showed OCD exhibited decreased dynamics of degree centrality in IC38 (P = 0.003) compared with HC, which showed a negative correlation with clinical scores in OCD. While SZ showed decreased dynamics of degree centrality in IC76 (located in sensory motor network) compared with OCD (P=0.009), which showed a positive correlation with clinical scores in SZ (Figure 2).
These changes are suggestive of disorder-specific alternation of static and dynamic brain topological organization in OCD and SZ.
Obsessive-compulsive disorder (OCD) and schizophrenia (SZ) are both severe psychiatric disorders. Though these two disorders have distinct typical symptoms, there are partial polygenic overlap and comorbidity between the two disorders. However, few studies have explored the shared and disorder-specific brain function underlying the neural pathophysiology of the two disorders, especially in the aspect of dynamics.
To explore the abnormal characteristics of the dynamic functional connectivity (dFC) in OCD and SZ as well as the association between dFC metrics and symptom severity.
The resting state functional magnetic resonance imaging data of 31 patients with OCD, 49 patients with SZ, and 45 healthy controls were analyzed using independent component analysis to obtain independent components (ICs) and assigned them into eight brain networks (Figure 1), then used the sliding-window approach to generate dFC matrices. Using k-means clustering, we obtained three reoccurring dFC states (Figure 2), and state transition metrics were obtained
In a sparsely connected state (state 1), SZ showed both increased fractional time and mean dwell time than controls (P=0.047 and P=0.033) and OCD (P=0.001 and P=0.003). In a state characterized by negative FC between networks (state 2), OCD showed both increased fractional time and mean dwell time than controls (P=0.032 and P=0.013) and SZ (P=0.005 and P=0.003). Moreover, the fractional time of state 2 was positively correlated with anxiety scores in OCD (r=0.535, P=0.021, FDR corrected) (Figure 3).
OCD and SZ patients showed distinct alternations of brain functional dynamics.
There are growing efforts to mine public and common-sense semantic network databases for engineering design ideation stimuli. However, there is still a lack of design ideation aids based on semantic network databases that are specialized in engineering or technology-based knowledge. In this study, we present a new methodology of using the Technology Semantic Network (TechNet) to stimulate idea generation in engineering design. The core of the methodology is to guide the inference of new technical concepts in the white space surrounding a focal design domain according to their semantic distance in the large TechNet, for potential syntheses into new design ideas. We demonstrate the effectiveness in general, and use strategies and ideation outcome implications of the methodology via a case study of flying car design idea generation.
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.
Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.
We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.
Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.
These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.
Introduction: The Canadian College of Family Medicine Emergency Medicine Program (CCFP-EM) program is a 1-year enhanced skills program available to family medicine graduates interested in emergency medicine. Strong mentorship relationships were thought to assist residents with navigating the challenges of this program. Over the past 4 years, the CCFP-EM program at one academic centre initiated a novel mentorship program that matches residents with staff physicians in three areas of mentorship: clinical, research, and personal. This study aimed to determine the program success and areas for improvement. Methods: We conducted a cross-sectional study through an online survey distributed to all CCFP-EM residents and staff mentors from July 2015 to June 2019. Surveys included questions on the degree of satisfaction with the mentorship program, perceptions on the mentor/mentee experience, and areas for improvement. We asked staff and residents to rate their level of satisfaction with each mentorship component. Descriptive statistics were used to analyze satisfaction levels. Open-ended responses were analyzed for common themes. Results: 51.3% (19/37) of residents and 63.6% (35/55) of staff participated. For clinical mentorship, 68.5% of residents and 96.0% of staff rated the program as satisfactory/outstanding. For research mentorship, 73.7% of residents and 76.5% of staff rated the program as satisfactory/outstanding. The personal mentorship program was rated satisfactory/outstanding by 72.2% of residents and 95.3% of staff. Analysis for common themes revealed that continuity of support, development of autonomy, and opportunity for direct teaching were the main areas valued by residents. However, scheduling, teaching time, and mentor-mentee compatibility were the main challenges for residents. For mentors, scheduling was a main barrier to clinical mentorship, time constraint and resident commitment were the barriers to research mentorship, and resident engagement was the main barrier to personal mentorship. When asked which component(s) of mentorship should be continued for future residents, “personal mentorship only” was the most popular choice for staff (37.1%), while “mentorship in all three areas” was the most popular choice for residents (47.4%). Conclusion: Mentorship is an important aspect of the CCFP-EM program valued by staff and residents alike. Utilizing resident and staff feedback will allow for continuous improvement to the mentorship program.
Increasing evidence indicates that major depressive disorder (MDD) is associated with cognitive as well as mood disturbances.
To evaluate cognitive function and white matter structure, resting-state brain function in first-episode, treatmentnaive patients with MDD.
To explore brain structure and function mechanisms of cognitive impairment in MDD.
46 Han Chinese MDD patients aged 18–45 year and 46 controls were assessed by a series of validated test procedures.Then, 30 patients and 30 controls were obtained by MRI scan.White matter abnormalities evaluated using diffusion tensor imaging (DTI) were analyzed using tract based spatial statistics (TBSS) and resting-state brain function was evaluated using regional homogeneity (ReHo) analysis.
Cognitive impairment in patients with MDD was demonstrated by reduced accuracy in the Wisconsin Card Sorting test (WSCT) and to a lesser extent the Continuous Performance test (CPT) and Trail Making tests (TMT). White matter abnormalities found in the left cerebellum, and resting-state abnormalities present in the left inferior parietal gyrus, left anterior cingulate nucleus and left hippocampal gyrus were associated with impaired performance in the WSCT and CPT tests. We also showed that poor WSCT performance was associated with increased interconnectivity between the left ventral anterior cingulate nucleus and the medial frontal lobe areas.
The present study indicates cognitive disturbances in patients with MDD are associated with white matter and resting-state changes and altered interconnections in specific brain areas.
This study aimed at comparing the factors associated with the natural progression between typical progressors (TPs) and rapid progressors (RPs) in HIV-infected individuals. A retrospective study was conducted on 2095 eligible HIV-infected individuals from 1995 to 2016 in a high-risk area of Henan Province, China. Propensity score matching was used to balance covariates, and the conditional logistic regression analyses were performed to explore the factors of natural disease progression among HIV infectors. A total of 379 pairs of RPs and TPs were matched. The standardised difference values of all covariates were less than 10%. HIV-infected individuals transmitted through sexual transmission (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.36–0.85) were more likely to progress to AIDS compared with those infected through contaminated blood. Older age at diagnosis of HIV-infected individuals (OR 0.72, 95% CI 0.58–0.89) exhibited a faster progression to AIDS. HIV-infected individuals identified through a unique survey (OR 7.01, 95% CI 2.99–16.44) were less likely to progress to AIDS compared with those identified through medical institutions. HIV-infected individuals who had higher baseline CD4+T cell counts (OR 3.37, 95% CI 2.59–4.38) had a slower progression to AIDS. These findings provide evidence for natural disease progression from HIV to AIDS between TPs and RPs.
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.
The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.
Textual idea data from online crowdsourcing contains rich information of the concepts that underlie the original ideas and can be recombined to generate new ideas. But representing such information in a way that can stimulate new ideas is not a trivial task, because crowdsourced data are often vast and in unstructured natural languages. This paper introduces a method that uses natural language processing to summarize a massive number of idea descriptions and represents the underlying concept space as word clouds with a core-periphery structure to inspire recombinations of such concepts into new ideas. We report the use of this method in a real public-sector-sponsored project to explore ideas for future transportation system design. Word clouds that represent the concept space underlying original crowdsourced ideas are used as ideation aids and stimulate many new ideas with varied novelty, usefulness and feasibility. The new ideas suggest that the proposed method helps expand the idea space. Our analysis of these ideas and a survey with the designers who generated them shed light on how people perceive and use the word clouds as ideation aids and suggest future research directions.
Optimizing the dietary calcium (Ca) level is essential to maximize the eggshell quality, egg production and bone formation in poultry. This study aimed to establish the Ca requirements of egg-type duck breeders from 23 to 57 weeks of age on egg production, eggshell, incubation, tibial, plasma and ovary-related indices, as well as the expression of matrix protein-related genes. Totally, 450 Longyan duck breeders aged 21 weeks of age were allotted randomly into five treatments, each with six replicates of 15 individually caged birds. The data collection started from 23 weeks of age and continued over the following 35 weeks. The five groups corresponded to five dietary treatments containing either 2.8%, 3.2%, 3.6%, 4.0% or 4.4% Ca. The tested dietary Ca levels increased (linear, P <0.01) egg production and egg mass, and linearly improved (P <0.01) the feed conversion ratio (FCR). Increasing the dietary Ca levels from 2.8% to 4.4% increased (P <0.01) the eggshell thickness and eggshell content. The tested Ca levels showed a quadratic effect on eggshell thickness and ovarian weight (P <0.01); the highest values were obtained with the Ca levels 4.0% and 3.6%, respectively. Dietary Ca levels affected the small yellow follicles (SYF) number and SYF weight/ovarian weight, and the linear response (P <0.01) was significant vis-à-vis SYF number. In addition, dietary Ca levels increased (P <0.05) the tibial dry weight, breaking strength, mineral density and ash content. Plasma and tibial phosphorus concentration exhibited a quadratic (P <0.01) response to dietary Ca levels. Plasma calcitonin concentration linearly (P <0.01) increased as dietary Ca levels increased. The relative expression of carbonic anhydrase 2 in the uterus rose (P <0.01) with the increment of dietary Ca levels, and the highest value was obtained with 3.2% Ca. In conclusion, Longyan duck breeders fed a diet with 4.0% Ca had superior eggshell and tibial quality, while those fed a diet with 3.6% Ca had the heaviest ovarian weights. The regression model indicated that the dietary Ca levels 3.86%, 3.48% and 4.00% are optimal levels to obtain maximum eggshell thickness, ovarian weight and tibial mineral density, respectively.
Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P < 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.