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The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact.
A social network is a valuable resource in later life. Therefore, the current study aims to investigate whether social networks within homes and neighbourhoods are associated with older adults’ daily fruit and vegetable consumption.
Cross-sectional secondary data analysis.
A nationally representative sample of 6865 community-dwelling older adults over age 53 in the Health and Retirement Study – Health Care and Nutrition Survey.
Older adults who lived alone with no children or friends nearby had the lowest fruit and vegetable consumption. However, the daily fruit and vegetable consumption of respondents who lived alone and had children or friends nearby or those who lived with someone and had no children or friends nearby was not statistically different from those who lived with someone and had children or friends nearby. This suggests that having a social network either at home or in the neighbourhood complements the absence of living with someone or having children or friends nearby and attenuates the negative association between limited social networks and daily fruit and vegetable consumption. A greater decrease in the number of fruits and vegetables consumed was observed among men when they lived alone with no children or friends nearby.
Special attention should be given to older adults with limited social networks, especially older adults living alone with no children or friends nearby. Provision of help with grocery shopping and meal preparation as well as social support networks and more opportunities that can improve social engagement appear to be necessary.
The present study investigated the association between fibre degradation and the concentration of dissolved molecular hydrogen (H2) in the rumen. Napier grass (NG) silage and corn stover (CS) silage were compared as forages with contrasting structures and degradation patterns. In the first experiment, CS silage had greater 48-h DM, neutral-detergent fibre (NDF) and acid-detergent fibre degradation, and total gas and methane (CH4) volumes, and lower 48-h H2 volume than NG silage in 48-h in vitro incubations. In the second experiment, twenty-four growing beef bulls were fed diets including 55 % (DM basis) NG or CS silages. Bulls fed the CS diet had greater DM intake (DMI), average daily gain, total-tract digestibility of OM and NDF, ruminal dissolved methane (dCH4) concentration and gene copies of protozoa, methanogens, Ruminococcus albus and R. flavefaciens, and had lower ruminal dH2 concentration, and molar proportions of valerate and isovalerate, in comparison with those fed the NG diet. There was a negative correlation between dH2 concentration and NDF digestibility in bulls fed the CS diet, and a lack of relationship between dH2 concentration and NDF digestibility with the NG diet. In summary, the fibre of CS silage was more easily degraded by rumen microorganisms than that of NG silage. Increased dCH4 concentration with the CS diet presumably led to the decreased ruminal dH2 concentration, which may be helpful for fibre degradation and growth of fibrolytic micro-organisms in the rumen.
Developing alternatives to antibiotics is an urgent need in livestock production. Antimicrobial peptides (AMPs) are regarded as powerful antibiotic substitutes (ASs) because AMPs have broad-spectrum antimicrobial activities and growth-promoting ability. Here, we aimed to comprehensively assess the effects of AMPs on the growth performance, diarrhea rate, intestinal morphology and immunity of healthy or challenged piglets, compared with an antibiotics group or negative control group. We performed a set of meta-analyses of feeding trials from database inception to 27 May 2019. Among the 1379 identified studies, 20 were included in our meta-analyses (56 arms and 4067 piglets). The meta-analyses revealed that (1) compared with the negative control group, AMPs significantly improved the healthy piglets’ average daily gain (ADG), average daily feed intake (ADFI), gain : feed ratio (G/F), levels of immune globulin (Ig) IgM and IgG, and intestinal villus height : crypt depth ratio (V/C) (P < 0.05). Meanwhile, AMPs significantly increased the challenged piglets’ ADG, ADFI, G/F and V/C of the jejunum and ileum, and notably deceased the diarrhea rate (P < 0.05); (2) compared with antibiotics group, the effects of AMPs were slightly weaker than those of antibiotics in the healthy piglets, but AMPs have similar effects to those of antibiotics in challenged piglets. In a higher purity, the optimal dose of AMPs may be approximately 0.01%. Our findings indicate that AMPs can improve piglet growth performance, enhance immunity, benefit intestinal morphology and decrease the diarrheal rate. AMPs could be great ASs especially under infection conditions.
Antibiotics are commonly used in intensive care units (ICUs), yet differences in antibiotic use across ICUs are unknown. Herein, we studied antibiotic use across ICUs and examined factors that contributed to variation.
We conducted a retrospective cohort study using data from Ontario’s Critical Care Information System (CCIS), which included 201 adult ICUs and 2,013,397 patient days from January 2012 to June 2016. Antibiotic use was measured in days of therapy (DOT) per 1,000 patient days. ICU factors included ability to provide ventilator support (level 3) or not (level 2), ICU type (medical-surgical or other), and academic status. Patient factors included severity of illness using multiple-organ dysfunction score (MODS), ventilatory support, and central venous catheter (CVC) use. We analyzed the effect of these factors on variation in antibiotic use.
Overall, 269,351 patients (56%) received antibiotics during their ICU stay. The mean antibiotic use was 624 (range 3–1460) DOT per 1,000 patient days. Antibiotic use was significantly higher in medical-surgical ICUs compared to other ICUs (697 vs 410 DOT per 1,000 patient days; P < .0001) and in level 3 ICUs compared to level 2 ICUs (751 vs 513 DOT per 1,000 patient days; P < .0001). Higher antibiotic use was associated with higher severity of illness and intensity of treatment. ICU and patient factors explained 47% of the variation in antibiotic use across ICUs.
Antibiotic use varies widely across ICUs, which is partially associated with ICUs and patient characteristics. These differences highlight the importance of antimicrobial stewardship to ensure appropriate use of antibiotics in ICU patients.
OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Available data suggest that sex hormone levels during puberty may affect symptom onset and expression, treatment responsiveness and outcomes in schizophrenia, whereas post-pubertal adolescents may have a similar clinical presentation and treatment response compared to adults with schizophrenia.
Post-hoc analyses were conducted to assess the similarity of short- and long-term efficacy between post-pubertal adolescents and adults with schizophrenia treated with aripiprazole.
Based on available European epidemiologic data, a cut-off age of 15 years was used to isolate a subgroup of mostly post-pubertal adolescents with schizophrenia in aripiprazole clinical studies. Outcome measures from this subgroup (ages 15-17; n=147) were then compared to outcomes from one adult study (n=853) on short and long-term measures of efficacy, including PANSS scores, response rates, and remission rates.
Comparable short and long-term treatment effects were observed on the PANSS total and subscale scores, demonstrated by overlapping 95% confidence intervals (mean change from baseline in PANSS total score (OC dataset): at week 6 in adults: -27,7; in adolescents 15-17 yr: -29,6; at week 30 in adults: -39,2; in adolescents 15-17 yr: -36). Percent of adolescents achieving response (defined as ≥ 30% decrease in PANSS total score from baseline) at 32 weeks (80,2%) on open label treatment was similar to that in adult studies at week 34 (80%) on double blind treatment (OC dataset).
Adolescents with schizophrenia (ages 15-17, mostly post-pubertal) demonstrate a positive treatment response in short-term and long-term studies which is similar to that observed in the adult patient population.
Agitation is a common presentation among patients hospitalized for an acute exacerbation of schizophrenia. Rapid and effective control of agitation is an important early treatment goal.
The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in reducing agitation in patients with an acute exacerbation of schizophrenia.
The analysis was performed on pooled data from 5 six-week, placebo-controlled trials in the subgroup of patients with an acute exacerbation of schizophrenia who met (n=773), or did not meet (n=754), criteria) for agitation (PANSS-Excited Component [EC] score ≥14 at baseline, Citrome, J Clin Psych 2007;68:1876-1885). Patients were randomized to fixed once-daily doses of lurasidone (40-160 mg).
The mean baseline PANSS-EC scores were similar for lurasidone vs. placebo in the high (16.7 vs. 16.8) and low (10.9 vs. 10.7) agitation subgroups. In the high agitation subgroup, treatment with lurasidone (vs. placebo) was associated with significantly greater improvement in PANSS-EC scores at days 3/4 (-2.0 vs. -1.3; p<0.001) and day 7 (-2.6 vs. -1.8; p<0.001). At week 6 endpoint, improvement on lurasidone vs. placebo was greater in the high vs. low agitation groups on the PANSS-EC score (effect size, 0.43 vs. 0.31), and comparable on the PANSS total score (effect size, 0.57 vs. 0.58).
In this pooled post-hoc analysis, treatment with lurasidone significantly reduced agitation by day 3/4 in patients hospitalized with an acute exacerbation of schizophrenia. The magnitude of improvement at week 6 was similar in both the high and low agitation groups.
The number of Korean smartphone users exceeded 40 million in 2015, in which roughly 1 in 5 university students were expected to be addicted to their smartphone. Of importance is that smartphone addiction negatively affects physical and mental well-being and health. Sleep problems associated with smartphone is also a serious public concern; but the evidence is lacking. The aim of this study is to investigate the association between smartphone addiction proneness and sleep problems in Korean university students.
We conducted an online-survey which received responses from 608 university students. All participants completed questionnaires on the Korean smartphone addiction scale (K-SAS), the Pittsburgh Sleep Quality Index (PSQI), and personal characteristics. Based on the scores of the K-SAS, university students were classified into two groups–the addiction proneness group and the normal-user group.
The addiction proneness groups had a higher PSQI score than the normal-user group (7.5 vs. 6.7, P-value < 0.0001). After adjustment for potential covariates (i.e., age, income, and smoking), PSQI scores was significantly increased in the addiction proneness groups (Beta coefficient = 0.69; 95% CI : 0.29 ∼ 1.09). The risk of sleep problems was more increased in the addiction proneness groups (odds ratio = 1.99; 95% CI: 1.33 ∼ 2.98) than the normal-user groups.
We found that the smartphone addiction proneness was associated with sleep problems in university students. Although our findings are further confirmed by elucidating causal relationships between smartphone uses and sleep habits, smartphone addiction proneness may be a risk factor for poor sleep quality.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Mindfulness based art therapy induces emotional relaxation in cancer patients and is a treatment known to improve psychological stability. The objective of this research was to evaluate the treatment effects of MBAT for breast cancer patients.
Twenty-four breast cancer patients were selected as subjects of the study. Two groups, the MBAT group and control group with 12 patients each, were randomly assigned. The patients in the MBAT group were given 12 sessions of treatments. To measure depression and anxiety, low scales of the Personality Assessment Inventory (PAI) was used. Health-related quality of life was evaluated using the European organization for research and treatment of cancer quality of life questionnaire (EORTC-QLQ-C30). The treatment results were analyzed using Ancova and two-way repeated measures Anova.
The results showed that depression and anxiety decreased significantly and health-related quality of life improved significantly in the MBAT group. In the control group, however, there was no significant change.
MBAT can be seen as an effective treatment method that improves breast cancer patients’ psychological stability and quality of life. Evaluation of treatment effects using program development and large-scale research for future clinical application is needed.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992–1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997–2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies.
Catheter-associated urinary tract infections in 592 hospitals immediately declined after federal value-based incentive program implementation, but this was fully attributable to a concurrent surveillance case definition revision. Post revision, more hospitals had favorable standardized infection ratios, likely leading to artificial inflation of their performance scores unrelated to changes in patient safety.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
Solar coronal dimmings have been observed extensively in the past two decades and are believed to have close association with coronal mass ejections (CMEs). Recent study found that coronal dimming is the only signature that could differentiate powerful flares that have CMEs from those that do not. Therefore, dimming might be one of the best candidates to observe the stellar CMEs on distant Sun-like stars. In this study, we investigate the possibility of using coronal dimming as a proxy to diagnose stellar CMEs. By simulating a realistic solar CME event and corresponding coronal dimming using a global magnetohydrodynamics model (AWSoM: Alfvén-wave Solar Model), we first demonstrate the capability of the model to reproduce solar observations. We then extend the model for simulating stellar CMEs by modifying the input magnetic flux density as well as the initial magnetic energy of the CME flux rope. Our result suggests that with improved instrument sensitivity, it is possible to detect the coronal dimming signals induced by the stellar CMEs.
The formation of Low mass X-ray binaries (LMXB) is favored within dense stellar systems such as Globular Clusters (GCs). The connection between LMXB and Globular Clusters has been extensively studied in the literature, but these studies have always been restricted to the innermost regions of galaxies. We present a study of LMXB in GCs within the central 1.5 deg2 of the Fornax cluster with the aim of confirming the existence of a population of LMXB in intra-cluster GCs and understand if their properties are related to the host GCs, to the environment or/and to different formation channels.
Whole eggs are rich sources of several micronutrients. However, it is not well known how egg consumption contributes to overall nutrient adequacy and how it may relate to CVD risk factors. Therefore, the present study aimed to determine how whole egg consumption contributes to nutrient intakes and to assess its association with CVD risk factors in US adults.
The study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2012, a nationally representative survey of the US civilian population.
Adults who completed two dietary recalls and provided information on relevant sociodemographic factors were included in the study (n 21 845).
Approximately 73 % of adults were classified as whole egg consumers. Egg consumption was associated with greater intakes of protein, saturated fat, mono- and polyunsaturated fats, Fe, Zn, Ca, Se, choline, and several other vitamins and minerals. Egg consumption was associated with a higher likelihood of meeting or exceeding recommendations for several micronutrients. Egg intake was positively associated with dietary cholesterol consumption, but not with serum total cholesterol (TC) when adjusted for multiple potential confounders. In multiple linear regression analyses, TAG, TAG:HDL-cholesterol and TC:HDL-cholesterol were significantly lower with greater egg consumption. Egg consumption had no significant relationship with LDL-cholesterol or C-reactive protein, but was associated with higher BMI and waist circumference.
Whole eggs are important dietary contributors of many nutrients and had either beneficial or non-significant associations with most CVD risk biomarkers examined.
OBJECTIVES/SPECIFIC AIMS: The cellular mechanisms that underlie the IFNβ/α ratio that predicts response are not known. Effects of IFN on single immune cells may be masked in whole blood or mixed cell populations. By studying the effect of IFNβ/α activity ratio on individual monocytes, we can determine the functional impact of the IFN ratio and suggest the cellular mechanisms that underlie response/non-response to TNFi therapy in RA. METHODS/STUDY POPULATION: We used single cell analysis to investigate whether monocyte gene expression differs significantly between RA patients according to their pre-TNFi serum IFN-β/α ratio. Single classical (CL) and non-classical (NC) blood-derived monocytes were isolated from 15 seropositive RA subjects prior to biologic therapy. Subjects were grouped by pre-TNFi serum IFN-β/α ratio into two groups, those with a high IFN-β/α ratio (≥1.3, n = 6) and those with a low IFN-β/α ratio (<1.3, n = 9). 87 target genes were analyzed. Genes that varied significantly between the groups by categorical analyses were tested in multivariate logistic regression models. RESULTS/ANTICIPATED RESULTS: Every participant was seropositive for rheumatoid factor and antibodies to cyclic citrullinated peptide. Among the participants in the groups, there were no significant differences in age or DAS scores (P>0.05). The treatments were comparable and none were being treated with biologic therapy. There were striking differences in monocyte gene expression between patients with pre-treatment blood IFNβ/α activity <1.3 and ≥1.3. Expression of (1) key type I IFN pathway genes (JAK1, STAT2, IFIT2, IFIH1, PRDM1); (2) IL12; (3) CD36; and (4) CTLA4 were the strongest differentiators between groups (p<0.0001 for each, corrected for multiple comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: In this study we were able to measure gene expression in single monocytes from seropositive RA patients prior to biologic treatment. Within-cell co-expression patterns demonstrate biological differences in monocytes of RA patients with an IFNβ/α ≥1.3, the ratio of type I IFNs which predicts non-response to TNFi. The data suggest that there may be differential IFN production and pathway activation in patients who do not respond to TNFi. The increased expression of CD36 in monocytes from RA patients with high IFN β/α activity may be a reflection of increased “foam cells” in the inflamed tissue of patients who do not respond to TNFi. Enrichment of CTLA4 in those with high serum IFNβ/α suggests that CTLA4-Ig may be less likely to be an effective alternative for someone who is not likely to respond to TNFi. Current work includes determining whether the peripheral blood findings reflect altered cellular composition, type I IFN production and signaling in the synovium. Significance: This work will help to develop a more individualized approach to therapy in RA and determine an immunological basis of response/non-response to TNFi.