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Perceived loneliness, an increasingly prevalent social issue, is closely associated with major depressive disorder (MDD). However, the neural mechanisms previously implicated in key cognitive and affective processes in loneliness and MDD still remain unclear. Such understanding is critical for delineating the psychobiological basis of the relationship between loneliness and MDD.
We isolated the unique and interactive cognitive and neural substrates of loneliness and MDD among 27 MDD patients (mean age = 51.85 years, 20 females), and 25 matched healthy controls (HCs; mean age = 48.72 years, 19 females). We assessed participants' behavioral performance and neural regional and network functions on a Stroop color-word task, and their resting-state neural connectivity.
Behaviorally, we found greater incongruence-related accuracy cost in MDD patients, but reduced incongruence effect on reaction time in lonelier individuals. When performing the Stroop task, loneliness positively predicted prefrontal-anterior cingulate-parietal connectivity across all participants, whereas MDD patients showed a decrease in connectivity compared to controls. Furthermore, loneliness negatively predicted parietal and cerebellar activities in MDD patients, but positively predicted the same activities in HCs. During resting state, MDD patients showed reduced parietal-anterior cingulate connectivity, which again positively correlated with loneliness in this group.
We speculate the distinct neurocognitive profile of loneliness might indicate increase in both bottom-up attention and top-down executive control functions. However, the upregulated cognitive control processes in lonely individuals may eventually become exhausted, which may in turn predispose to MDD onset.
Given the range and reach of psychosocial support (PSS) interventions in humanitarian settings, within the continuum of mental health and psychosocial support services, evaluation of their impact is critical. Understanding stakeholders' perspectives on which PSS interventions of unknown effectiveness warrant rigorous evaluation is essential to identify research priorities. This project aimed to facilitate a process with stakeholders to reach consensus on PSS interventions that are of high priority for further research based on existing evidence and stakeholders' opinions.
Interviews with 109 stakeholders working on PSS programming in humanitarian settings served as the foundation for two in-person regional meetings and four webinars. Nominal Group Technique (NGT) was used to develop a priority PSS program list. The top five priorities from each meeting were combined for a final online survey distributed globally.
Seventy participants across six meetings contributed to the prioritization process. Eighty-seven individuals completed the final online survey. ‘Community based PSS’ was the top-ranked research priority, followed by PSS integrated into basic services, providing PSS to caregivers to improve child wellbeing, PSS-focused gender-based violence programming, and classroom-based PSS interventions.
NGT and online surveys were effective methods to engage stakeholders in a priority setting exercise to development a research agenda. Information from this stage of the project will be combined with findings from a concurrent systematic review to form the base of a second phase of work, which will include the development and implementation of a research strategy to strengthen the evidence base for those prioritized interventions.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
In this study, the pull-in phenomenon of a Nano-actuator is investigated employing a nonlocal Bernoulli-Euler beam model with clamped-clamped conditions. The model accounts for viscous damping, residual stresses, the van der Waals (vdW) force and electrostatic forces with nonlocal effects. The hybrid differential transformation/finite difference method (HDTFDM) is used to analyze the nonlocal effects on a graphene sheet nanobeam, which is electrostatically actuated under the influence of the coupling effect, the von Kármán nonlinear strains and the fringing field effect. The pull-in voltage as calculated by the presented model deviates by no more than 0.29% from previous literature, verifying the validity of the HDTFDM. Furthermore, the nonlocal nonlinear behavior of the electrostatically actuated nanobeam is investigated, and the effects of viscous damping, residual stresses, and length-gap ratio are examined in detail. Overall, the results reveal that small scale effects significantly influence the characteristics of the graphene sheet nanobeam actuator.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Polymeric conjugated materials are very promising for developing future soft material-based semiconductors, conductors, electronic and optoelectronic devices due to their inherent advantages such as flexibility, low-cost, ease of processability, and decreased harmful waste. Like their inorganic counterparts, the addition of certain dopants can significantly alter the electronic and optoelectronic properties of the host conjugated polymers or composites allowing modification for a variety of electronic/optoelectronic applications. One way to improve device performance is through the process of thermal annealing. Annealing allows for polymer matrices to self-assemble into a lower energy state which typically leads to increased crystallinity and higher charge mobility. In this work, we plan to evaluate the effects of annealing on doped P3HT films to understand its effects on optoelectronic and electronic properties focusing solely on crystallinity and charge carriers. Further understanding of the connection between annealing and doping in polymeric conjugated materials and thermoelectric properties will allow for an increase net output from multi-function materials and devices.
Antimicrobial stewardship programs typically use days of therapy to assess antimicrobial use. However, this metric does not account for the antimicrobial spectrum of activity. We applied an antibiotic spectrum index to a population of very-low-birth-weight infants to assess its utility to evaluate the impact of antimicrobial stewardship interventions.
For decades, fructose intake has been recognised as an environmental risk for metabolic syndromes and diseases. Here we comprehensively examined the effects of fructose intake on mice liver transcriptomes. Fructose-supplemented water (34 %; w/v) was fed to both male and female C57BL/6N mice at their free will for 6 weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEG) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. As a result, we identified eighty-nine down-regulated and eighty-eight up-regulated mRNA in fructose-fed mice livers. These DEG were subjected to bioinformatics analysis tools in which DEG were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes, while fructose suppresses the AhR signalling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signalling through modulating expressions of transcription factor (AhR nuclear translocator; Arnt) and upstream regulators (Ncor2, and Rb1). Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signalling pathway in C57BL/6N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on (1) other types of carcinogens and (2) inflammation-inducing agents (or even diets such as a high-fat diet), to find implications of fructose-induced AhR suppression.
Calls for a return to a traditional method of lawmaking known as “regular order” have proliferated as unorthodox lawmaking has grown more dominant in Congress. Proponents claim regular order enhances deliberation on legislation. This chapter examines deliberation under one form of regular order: open rules permitting unlimited amending in the House of Representatives. We find evidence of substantial minority influence on the inputs and outputs of the appropriations process. Regular order gives the minority party members the opportunity to present and win adoption of their policy proposals. Our evidence also shows that ideological extremists play an outsized role in debate. They offer more amendments than other members, and their amendments tend to win less support and face defeat more often than moderates. The paradox of regular order is that it simultaneously offers the opportunity for bipartisan deliberation over legislation while exposing the majority party to problems that may make its management of the floor more difficult.
Polymeric conjugated materials are convenient for developing future soft-material-based semiconductors, conductors, electronic and optoelectronic devices due to their inherent features. Similar to their inorganic counterparts, the addition of certain minority molecules, or dopants, to polymeric conjugated materials can significantly alter the electronic and optoelectronic properties of the host conjugated polymers or composites. This allows for tunability of a variety of electronic and optoelectronic applications. One way to improve device performance is through the process of thermal annealing. Annealing allows for a polymer matrix to self-assemble into a lower energy state, which leads to an increase in crystallinity and higher charge mobility. Previous research does not explicitly define how dopants can affect this process. This study involves an evaluation of the effects of annealing with doped P3HT films to demonstrate changes in optoelectronic and electronic properties.
In 2010, South Africa (SA) hosted the Fédération Internationale de Football Association (FIFA) World Cup (soccer). Emergency Medical Services (EMS) used the SA mass gathering medicine (MGM) resource model to predict resource allocation. This study analyzed data from the World Cup and compared them with the resource allocation predicted by the SA mass gathering model.
Prospectively, data were collected from patient contacts at 9 venues across the Western Cape province of South Africa. Required resources were based on the number of patients seeking basic life support (BLS), intermediate life support (ILS), and advanced life support (ALS). Overall patient presentation rates (PPRs) and transport to hospital rates (TTHRs) were also calculated.
BLS services were required for 78.4% (n = 1279) of patients and were consistently overestimated using the SA mass gathering model. ILS services were required for 14.0% (n = 228), and ALS services were required for 3.1% (n = 51) of patients. Both ILS and ALS services, and TTHR were underestimated at smaller venues.
The MGM predictive model overestimated BLS requirements and inconsistently predicted ILS and ALS requirements. MGM resource models, which are heavily based on predicted attendance levels, have inherent limitations, which may be improved by using research-based outcomes.
Background: This is an updated on-line survey of the awareness and knowledge of stroke and heart disease amongst Chinese-Canadians carried out in 2017. Methods: 1001 randomnly selected Chinese-Canadians from Toronto and Vancouver area. Results: 46% were > 45 years old and male to female ratio was: 49.3 : 50.8, with native language being Cantonese in 40%, Mandarin 24% and 31% English. 82% were Canadian citizens and 31% had been in Canada < 10 years. 44% were from Mainland China, 37% Hong Kong , 6% Taiwan and 12% were borned in Canada. 85% were able to name at least one symptom of heart attack (p=0.005) while 80% were able to name at least one symptom of stroke (p=0.0008). 85% would call 911 in response to symptoms of heart attack or stroke compared to only 20% in a previous 2004 telephone survey (p=0.00001) . Conclusions: There is a dramatic improvement in the awareness and knowledge of stroke and heart disease amongst Chinese-Canadians compared to a previous telephone survey in 2004. This significant change could be due to difference in survey technique, but these improvements could also be due to the ongoing health promotion efforts by the Chinese-Canadian Council in support of the Heart & Stroke Foundation.
Background: Surveillance by serial magnetic resonance imaging (MRI) is important in the management of diffuse low-grade gliomas (LGGs). Radiological interpretations of LGG scans, however, are typically qualitative and difficult to use clinically. Methods: We retrospectively compared radiological interpretations of LGG growth/stability to volume change measured by manual segmentation. Tumour diameter was measured to evaluate methods for assessing glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumour diameter/ellipsoid method. Results: Tumours evaluated as stable by radiologists grew a median 5.1 mL (11.1%) relative to the comparison scan. Those evaluated as having grown increased by 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate segmented volumes, and overestimation error increased with tumour size. Agreement with segmented volume improved from a mean difference of 17.6 to 4.5 to 3.9 mm for diameter and from 104.0 to 25.3 to 15.9 mL for volume with measurements in one, two, and three dimensions. Conclusions: Given evidence that LGG volume and growth are prognostic factors, lesions should be accurately measured. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. Volumetric analysis remains the gold standard for growth assessment, but diametric measurements in three dimensions may be an acceptable alternative.