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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Social cognitive deficits can have many negative consequences, spanning social withdrawal to psychopathology. Prior work has shown that child maltreatment may associate with poorer social cognitive skills in later life. However, no studies have examined this association from early childhood into adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4,438), we examined the association between maltreatment (caregiver physical or emotional abuse; sexual or physical abuse), assessed repeatedly (every 1–3 years) from birth to age 9, and social cognitive skills at ages 7.5, 10.5, and 14 years. We evaluated the role of both the developmental timing (defined by age at exposure) and accumulation of maltreatment (defined as the number of occasions exposed) using a least angle regression variable selection procedure, followed by structural equation modeling. Among females, accumulation of maltreatment explained the most variation in social cognitive skills. For males, no significant associations were found. These findings underscore the importance of early intervention to minimize the accumulation of maltreatment and showcase the importance of prospective studies to understand the development of social cognition over time.
To compare the nutritional quality of children’s combination meals offered at large US chain restaurants characterised by three versions – default (advertised), minimum (lower-energy) and maximum (higher-energy).
We identified default children’s meals (n 92) from online restaurant menus, then constructed minimum and maximum versions using realistic additions, substitutions and/or portion size changes for existing menu items. Nutrition data were obtained from the MenuStat database. Bootstrapped linear models assessed nutrition differences between meal versions and the extent to which meal components (main dish, side dish, beverage) drove differences across versions. For each version, we examined the proportion of meals meeting the Guidelines for Responsible Food Marketing to Children.
Twenty-six fast-food and fast-casual restaurants, in 2017.
Nutrient values differed significantly across meal versions for energy content (default 2443 kJ (584 kcal), minimum 1674 kJ (400 kcal), maximum 3314 kJ (792 kcal)), total fat (23, 17, 33 g), saturated fat (8, 6, 11 g), Na (1046, 915, 1287 mg) and sugar (35, 14, 51 g). The substitution of lower-energy beverages resulted in the greatest reduction in energy content (default to minimum, −418 kJ (−100 kcal)) and sugar (−20 g); choosing lower-energy side dishes resulted in the greatest reduction in total fat (default to minimum, −4 g), saturated fat (−1·1 g) and Na (−69 mg). Only 3 % of meals met guidelines for all nutrients.
Realistic modifications to children’s combination meals using existing menu options can significantly alter a meal’s nutrient composition. Promoting lower-energy items as the default option, especially for beverages and side dishes, has a potential to reduce fat, saturated fat and/or sugar in children’s meals.
Innovation Concept: High-acuity, low-occurrence (HALO) procedures require skilled performance as they treat life-threatening conditions and are associated with significant morbidity when performed incorrectly. Simulation has proven useful for deliberate practice in a low stake setting. Tube thoracostomy is amendable to this approach. Commercially available trainers exist but often have limited realism and are prohibitively expensive particularly to non-academic centers. Three-dimensional (3D) printing produces models suitable for simulation, but no current simulator has been developed and validated for tube thoracostomy. The aim of this study was to develop such, a 3D-printed low-fidelity simulator validated for the simulation-based instruction of tube thoracostomy. Methods: The development of the simulator followed an iterative design cycle with collaboration between a design team and an emergency medicine expert. Its validity (face and content) was tested through hands-on practice and surveys completed by 15 acute-care practitioners. Participants performed the procedure on the simulator and then provided feedback through a mixed quantitative/qualitative product evaluation survey on appearance, realism (face validity) and value in procedural training (content validity). Mean values for overall appearance and content validity as a training tool were 4/5 and 4.3/5 respectively. All respondents felt the model was a useful adjunct. All but one stated it was a good replacement for pre-existing trainers. Curriculum, Tool, or Material: The model was initially printed in three parts using an Ultimaker 3 and Axiom Airwolf Dual 3D-printer. The ribcage was created using polylactic acid with polyvinyl alcohol support material. Printed sections were bonded using glue at interfaces requiring no flexibility. Flexible joints were made of varying amounts of thermoplastic polyurethane and thermoplastic elastomer. Skin overlay for the whole model was created with a cut out area for replaceable sections that subjects would incise to insert the chest tube. Skin was casted using platinum cured silicone in a 3D-printed mold. Total cost of all materials was roughly 80 CAD. Conclusion: The simulator was found to be a useful adjunct for the simulation-based practice of tube thoracostomy. As well, users found the model anatomically realistic and avoided high-cost and ethical issues. Further research will focus on optimization based on feedback and development into a multi-functional simulator for other HALO procedures.
There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive Ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
This was a 12 week rater blind placebo controlled study. All to gather 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using PANSS, CGI, GAF and AIMS.
Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual (TAU) on PANSS total score, although, this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Anti-inflammatory treatments have shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. This study has led to a larger SMRI-funded, double blind, randomized control trial.
Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antagonist that has limited effects on cytokine production. This presentation will address their efficacy and mechanism of action.
1) Update on trials with minocycline including our own positive finding on negative symptoms (PMID: 16959472)
2) Present new results with ondansetron and simvastatin summarised below.
Ondansetron (8mg) and simvastatin (40mg) vs placebos in 2x2 design (PMID: 23782463). Patients aged 18-65, stable treatment, DSM IV schizophrenia-related diagnosis. PANSS and cognition at 0,3,6 months.
The four cells of the 2x2 design contained 302 patients. The interaction between ondansetron and simvastatin was significant at p=.006 reflecting the lower scores in the 3 active treatment groups than in the P+P group. Ondansetron improved verbal (p=.007) and visual list learning (p=.02) with no other treatment effects on cognition.
Minocycline appears to benefit negative symptoms in early psychosis with a minor effect on cognition. Simvastatin had limited effects in our patients with established schizophrenia but its anti-inflammatory effects could be worth investigating in early psychosis. Ondansetron has a significant effect on new learning, which might be expected from its 5-HT3 antagonist properties. This may underlie a benefit on negative symptoms reported by others and us.
There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene–environment correlation.
The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0–17 years; ALSPAC) and at age 8 years (MoBa).
Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure.
Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment.
Neurobiological models of auditory verbal hallucination (AVH) have been advanced by symptom capture functional magnetic resonance imaging (fMRI), where participants self-report hallucinations during scanning. To date, regions implicated are those involved with language, memory and emotion. However, previous studies focus on chronic schizophrenia, thus are limited by factors, such as medication use and illness duration. Studies also lack detailed phenomenological descriptions of AVHs. This study investigated the neural correlates of AVHs in patients with first episode psychosis (FEP) using symptom capture fMRI with a rich description of AVHs. We hypothesised that intrusive AVHs would be associated with dysfunctional salience network activity.
Sixteen FEP patients with frequent AVH completed four psychometrically validated tools to provide an objective measure of the nature of their AVHs. They then underwent fMRI symptom capture, utilising general linear models analysis to compare activity during AVH to the resting brain.
Symptom capture of AVH was achieved in nine patients who reported intrusive, malevolent and uncontrollable AVHs. Significant activity in the right insula and superior temporal gyrus (cluster size 141 mm3), and the left parahippocampal and lingual gyri (cluster size 121 mm3), P < 0.05 FDR corrected, were recorded during the experience of AVHs.
These results suggest salience network dysfunction (in the right insula) together with memory and language processing area activation in intrusive, malevolent AVHs in FEP. This finding concurs with others from chronic schizophrenia, suggesting these processes are intrinsic to psychosis itself and not related to length of illness or prolonged exposure to antipsychotic medication.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We report a significant advance in thermally insulating transparent materials: silica-based monoliths with controlled porosity which exhibit the transparency of windows in combination with a thermal conductivity comparable to aerogels.
The lack of transparent, thermally insulating windows leads to substantial heat loss in commercial and residential buildings, which accounts for ~4.2% of primary US energy consumption annually. The present study provides a potential solution to this problem by demonstrating that ambiently dried silica aerogel monoliths, i.e., ambigels, can simultaneously achieve high optical transparency and low thermal conductivity without supercritical drying. A combination of tetraethoxysilane, methyltriethoxysilane, and post-gelation surface modification precursors were used to synthesize ambiently dried materials with varying pore fractions and pore sizes. By controlling the synthesis and processing conditions, 0.5–3 mm thick mesoporous monoliths with transmittance >95% and a thermal conductivity of 0.04 W/(m K) were produced. A narrow pore size distribution, <15 nm, led to the excellent transparency and low haze, while porosity in excess of 80% resulted in low thermal conductivity. A thermal transport model considering fractal dimension and phonon-boundary scattering is proposed to explain the low effective thermal conductivity measured. This work offers new insights into the design of transparent, energy saving windows.
Both obesity and type 2 diabetes mellitus have been associated with excessive free sugar consumption. Increasingly, LCS are used to replace free sugar to reduce the energy density of the diet, whilst maintaining diet palatability. However, while experimental data suggest a beneficial effect of LCS on weight management and glycaemic control, data from free-living populations are contradictory and primarily use reported intakes of low-calorie sweetened beverages as a marker of overall LCS consumption. Therefore, a dietary assessment tool that reliably assesses overall LCS consumption and is applicable in large-scale epidemiological studies is desirable. This study aimed to validate an LCS-focused food frequency questionnaire (FFQ) for assessing habitual dietary intake of the LCS using the method of triads. Healthy adults were recruited at Ulster University, Coleraine (n = 120). A 65-item FFQ and a 4-day food diary (FD) were used to assess dietary intake of LCS with amounts based on maximum permitted levels for foods and beverages as per EU legislation. A novel urinary biomarker approach, developed by this research group, was used to objectively assess consumption of 5 commonly used LCS(1). The method of triads was used to validate the FFQ by evaluating the correlations between the FFQ, FD and the urinary biomarkers (reference method). A total of 110 participants (51 males, 59 females) completed all analyses. Median (IQR) total LCS consumption estimated from the FFQ, FD and urinary biomarker was 116.8 (24.9–303.3) mg/d, 27.8 (0.0–247.3) mg/d and 5.0 (0.6–34.9) mg/d respectively. Moderate correlations were observed between the FD and urinary biomarker (r = 0.471; P < 0.001) and between the FFQ and FD (r = 0.471; P < 0.001). There was a low correlation between the FFQ and urinary biomarker (r = 0.291; P < 0.001). Using the method of triads, the overall validity co-efficient for the FFQ was moderate (0.54). These preliminary results indicate potential for this LCS-focused FFQ as a method of assessing LCS consumption in free-living populations. However, as maximum permitted levels of LCS in foods and beverages were used to estimate LCS consumption from the FFQ and FD, they are likely to significantly overestimate actual LCS intakes as compared to the more reliable biomarker approach. Therefore, the FFQ ability to categorise individuals into low-, medium- and high LCS consumers will be tested. Further analysis is ongoing to assess the completeness of urine collections using PABA analysis and will also focus on individual LCS intake.
To characterize nontuberculous mycobacteria (NTM) associated with case clusters at 3 medical facilities.
Retrospective cohort study using molecular typing of patient and water isolates.
Veterans Affairs Medical Centers (VAMCs).
Isolation and identification of NTM from clinical and water samples using culture, MALDI-TOF, and gene population sequencing to determine species and genetic relatedness. Clinical data were abstracted from electronic health records.
An identical strain of Mycobacterium conceptionense was isolated from 41 patients at VA Medical Centers (VAMCs A, B, and D), and from VAMC A’s ICU ice machine. Isolates were initially identified as other NTM species within the M. fortuitum clade. Sequencing analyses revealed that they were identical M. conceptionense strains. Overall, 7 patients (17%) met the criteria for pulmonary or nonpulmonary infection with NTM, and 13 of 41 (32%) were treated with effective antimicrobials regardless of infection or colonization status. Separately, a M. mucogenicum patient strain from VAMC A matched a strain isolated from a VAMC B ICU ice machine. VAMC C, in a different state, had a 4-patient cluster with Mycobacterium porcinum. Strains were identical to those isolated from sink-water samples at this facility.
NTM from hospital water systems are found in hospitalized patients, often during workup for other infections, making attribution of NTM infection problematic. Variable NTM identification methods and changing taxonomy create challenges for epidemiologic investigation and linkage to environmental sources.
To understand price incentives to upsize combination meals at fast-food restaurants by comparing the calories (i.e. kilocalories; 1 kcal = 4·184 kJ) per dollar of default combination meals (as advertised on the menu) with a higher-calorie version (created using realistic consumer additions and portion-size changes).
Combination meals (lunch/dinner: n 258, breakfast: n 68, children’s: n 34) and their prices were identified from online menus; corresponding nutrition information for each menu item was obtained from a restaurant nutrition database (MenuStat). Linear models were used to examine the difference in total calories per dollar between default and higher-calorie combination meals, overall and by restaurant.
Ten large fast-food chain restaurants located in the fifteen most populous US cities in 2017–2018.
There were significantly more calories per dollar in higher-calorie v. default combination meals for lunch/dinner (default: 577 kJ (138 kcal)/dollar, higher-calorie: 707 kJ (169 kcal)/dollar, difference: 130 kJ (31 kcal)/dollar, P < 0·001) and breakfast (default: 536 kJ (128 kcal)/dollar, higher-calorie: 607 kJ (145 kcal)/dollar, difference: 71 kJ (17 kcal)/dollar, P = 0·009). Results for children’s meals were in the same direction but were not statistically significant (default: 536 kJ (128 kcal)/dollar, higher-calorie: 741 kJ (177 kcal)/dollar, difference: 205 kJ (49 kcal)/dollar, P = 0·053). Across restaurants, the percentage change in calories per dollar for higher-calorie v. default combination meals ranged from 0·1 % (Dunkin’ Donuts) to 55·0 % (Subway).
Higher-calorie combination meals in fast-food restaurants offer significantly more calories per dollar compared with default combination meals, suggesting there is a strong financial incentive for consumers to ‘upsize’ their orders. Future research should test price incentives for lower-calorie options to promote healthier restaurant choices.
The objective of this systematic review was to evaluate the efficacy of antibiotics to prevent or control colibacillosis in broilers. Studies found eligible were conducted controlled trials in broilers that evaluated an antibiotic intervention, with at least one of the following outcomes: mortality, feed conversion ratio (FCR), condemnations at slaughter, or total antibiotic use. Four electronic databases plus the gray literature were searched. Abstracts were screened for eligibility and data were extracted from eligible trials. Risk of bias was evaluated.
Seven trials reported eligible outcomes in a format that allowed data extraction; all reported results for FCR and one also reported mortality. Due to the heterogeneity in the interventions and outcomes evaluated, it was not feasible to conduct meta-analysis.
Qualitatively, for FCR, comparisons between an antibiotic and an alternative product did not show a significant benefit for either. Some of the comparisons between an antibiotic and a no-treatment placebo showed a numerical benefit to antibiotics, but with wide confidence intervals. The risk-of-bias assessment revealed concerns with reporting of key trial features.
The results of this review do not provide compelling evidence for or against the efficacy of antibiotics for the control of colibacillosis.
A systematic review and network meta-analysis (NMA) were conducted to address the question, ‘What is the efficacy of litter management strategies to reduce morbidity, mortality, condemnation at slaughter, or total antibiotic use in broilers?’ Eligible studies were clinical trials published in English evaluating the efficacy of litter management in broilers on morbidity, condemnations at slaughter, mortality, or total antibiotic use. Multiple databases and two conference proceedings were searched for relevant literature. After relevance screening and data extraction, there were 50 trials evaluating litter type, 22 trials evaluating litter additives, 10 trials comparing fresh to re-used litter, and six trials evaluating floor type. NMAs were conducted for mortality (61 trials) and for the presence or absence of footpad lesions (15 trials). There were no differences in mortality among the litter types, floor types, or additives. For footpad lesions, peat moss appeared beneficial compared to straw, based on a small number of comparisons. In a pairwise meta-analysis, there was no association between fresh versus used litter on the risk of mortality, although there was considerable heterogeneity among studies (I2 = 66%). There was poor reporting of key design features in many studies, and analyses rarely accounted for non-independence of observations within flocks.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.
Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease?’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.