To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
This work compares dose-volume constraints (DVCs) and tumour control predictions based on the average intensity projection (AVIP) to those on each phase of the four-dimensional computed tomography.
Materials and methods:
In this prospective study plans generated on an AVIP for nine patients with locally advanced non-small-cell lung cancer were recalculated on each phase. Dose-volume histogram (DVH) metrics extracted and tumour control probabilities (TCP) were calculated. These were evaluated by Bland–Altman analysis and Pearson Correlation.
The largest difference between clinical target volume (CTV) on the individual phases and the internal CTV (iCTV) on the AVIP was seen for the smallest volume. For the planning target volume, the mean of each metric across all phases is well represented by the AVIP value. For most patients, TCPs from individual phases are representative of that on the AVIP. Organ at risk metrics from the AVIP are similar to those seen across all phases.
Utilising traditional DVH metrics on an AVIP is generally valid, however, additional investigation may be required for small target volumes in combination with large motion as the differences between the values on the AVIP and any given phase may be significant.
Dunn identifies two foundational types of motivating experiences in earliest Christianity: postmortem appearances of Jesus and the first disciples’ Pentecost experiences. He regards the experiences of the apostle Paul as particularly illustrative of early Christianity, featuring the liberating power of the Spirit and of being “in Christ,” experiencing the Spirit of God as the Spirit of Jesus, and the shared experience of believers as members of the body of Christ.
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.
Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.
Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.
Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.
Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.
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.
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 smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).
Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.
In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.
Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.
OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.
Multiple studies have demonstrated that daily chlorhexidine gluconate (CHG) bathing is associated with a significant reduction in infections caused by gram-positive pathogens. However, there are limited data on the effectiveness of daily CHG bathing on gram-negative infections. The aim of this study was to determine whether daily CHG bathing is effective in reducing the rate of gram-negative infections in adult intensive care unit (ICU) patients.
We searched MEDLINE and 3 other databases for original studies comparing daily bathing with and without CHG. Two investigators extracted data independently on baseline characteristics, study design, form and concentration of CHG, incidence, and outcomes related to gram-negative infections. Data were combined using a random-effects model and pooled relative risk ratios (RRs), and 95% confidence intervals (CIs) were derived.
In total, 15 studies (n = 34,895 patients) met inclusion criteria. Daily CHG bathing was not significantly associated with a lower risk of gram-negative infections compared with controls (RR, 0.89; 95% CI, 0.73–1.08; P = .24). Subgroup analysis demonstrated that daily CHG bathing was not effective for reducing the risk of gram-negative infections caused by Acinetobacter, Escherichia coli, Klebsiella, Enterobacter, or Pseudomonas spp.
The use of daily CHG bathing was not associated with a lower risk of gram-negative infections. Further, better designed trials with adequate power and with gram-negative infections as the primary end point are needed.
To systematically review studies from Irish prisons that estimate the prevalence of major mental illness, alcohol and substance misuse, and homelessness at the time of committal.
Healthcare databases were searched for studies quantifying the point prevalence for each outcome of interest. Searches were augmented by scanning of bibliographies and searches of governmental and non-governmental websites. Proportional meta-analyses were completed for each outcome.
We found eight, six and five studies quantifying the point prevalence of major mental illness, substance misuse, and homelessness respectively. Considerable heterogeneity was found for each subgroup (except psychosis where substantial heterogeneity was observed) and random effects models were used to calculate pooled percentages. The pooled percentage for psychotic disorder was 3.6% [95% confidence interval (CI) 3.0–4.2%], for affective disorder 4.3% (95% CI 2.1–7.1%), for alcohol use disorder 28.3% (95% CI 19.9–37.4%), for substance use disorder 50.9% (95% CI 37.6–64.2%) and for those who were homeless on committal 17.4% (95% CI 8.7–28.4%).
Estimates for the prevalence of psychotic illness and substance abuse amongst Irish prisoners are in keeping with international estimates of morbidity in prisons, whilst those for affective disorders are lower. The prevalence of homelessness in committal to Irish prisons is higher than some international estimates. Rates for psychoses, alcohol and substance misuse as well as homelessness in Irish prisons are significantly higher than the general population prevalence of these vulnerabilities. A need for service development is discussed.
Non-axisymmetric endwalls in turbine stages have shown to be a robust method to improve the performance of turbines in both power generation and aero-derivative applications. Non-axisymmetric endwalls target the control of secondary flows and are designed using detailed computational fluid dynamics coupled with a variety of optimisation algorithms and utilising a number of objective functions according to the engine company or researcher's preference. These numerical predictions are often backed up by detailed measurements in linear and annular cascades and later proven in full-scale engine tests. Relatively little literature is available describing their performance in rotating test rigs or at conditions other than design, apart from that of the authors. This study comprehensively revisits the low-speed, model turbines used in the earlier study, replacing all of the 5-hole probe data with more accurate results and additional hot-film measurements. These results together with computational fluid dynamics solutions are used to show the success of the method across a large incidence range and to compare to earlier cascade results for a similar endwall and blade profile to establish the usefulness of cascade testing in this application. In addition, a comparison to two other off-design studies is made. Results indicate that the endwalls successfully improve the rotor total isentropic efficiency at all test conditions and that the improvement increases with increased turning in the blade row, from 0.5% to 1.8% across the incidence range. The results also compare well to the estimation of isentropic efficiency improvement that can be drawn from the cascade testing which stands at 1.55%.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
Hunger strikes in a custodial setting are complex to manage clinically, with associated legal and ethical complexities. Hunger strikes in Irish prisons have received, and are likely to continue to be the focus of, considerable media attention. Whilst there is an internationally accepted consensus ethical position, there is limited legal guidance available for psychiatrists to draw upon in such cases. In this paper, we review recent case-law and discuss the legal considerations in the management of prisoners on hunger strike.
The effects of shape and thickness of a tin surface layer and of the energy of a 170 ps neodymium:yttrium-aluminum-garnet laser pulse on the conversion efficiency (CE) into extreme ultraviolet emission in the 13.5 nm region is investigated. Whereas a CE of up to 1.16% into the 2% reflection band of multilayer Mo/Si optics was measured for a bulk Sn target at a laser energy of 25 mJ, significant CE enhancement up to 1.49% is demonstrated for a 200-nm-thick Sn layer on a microstructured porous alumina substrate.