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Probing hidden topology with quantum detectors
Get PDFWe consider the transition rate of a static Unruh-DeWitt detector in two (2+1)-dimensional black hole spacetimes that are isometric to the static Bañados-Teitelboim-Zanelli black hole outside the horizon but have no asymptotically locally anti-de Sitter exterior behind the horizon. The spacetimes are the RP2 geon, with spatial topology RP2\{point at infinity}, and the Swedish geon of Åminneborg et al., with spatial topology T2\{point at infinity}. For a conformal scalar field, prepared in the Hartle-Hawking-type state that is induced from the global vacuum on the anti-de Sitter covering space, we show numerically that the detector's transition rate distinguishes the two spacetimes, particularly at late exterior times, and we trace this phenomenon to the differences in the isometries that are broken by the quotient construction from the universal covering space. Our results provide an example in which information about the interior topology of a black hole is accessible to a quantum observer outside the black hole
Lending a helping hand to preterm infants: Randomized controlled trial of the impact of 'sticky mittens' on exploratory behavior and later development
Get PDFResearch with 3-month-old infants from the general population has shown benefits to their exploratory behavior from play involving ‘sticky mittens’. Sticky mittens are Velcro-covered mittens that are used with Velcro-covered toys to enable pre-reaching infants to grab and move toys simply by swatting at them. Our randomized controlled trial examined whether sticky mittens play, supervised by parents in the home environment, could similarly improve the exploratory behavior and later development of preterm infants. Participants (N = 62, 25–33 weeks of gestation) were recruited at 3 months of age corrected for prematurity and assigned randomly to either an intervention or active control group. For up to 5–10 min per day for three weeks, the intervention group used sticky mittens regularly while the control group instead watched their caregiver move the toys. Object-oriented exploratory behavior was evaluated immediately before and after the intervention, and caregivers completed questionnaires about their infant's development until 15 months' corrected age. Results showed that the intervention group made significantly greater gains than the control group in mouthing, F = 9.24, p = .004, ηp2 = 0.13, and bimanual exploration of the toys at or near the mouth, F = 8.07, p = .006, ηp2 = 0.12. However, the groups showed equivalent development over the next year as gauged by parent-report questionnaires p's > 0.05. While the sticky mittens intervention has immediate benefits for preterm infants' exploratory behavior, more research is needed before conclusions can be drawn regarding the longer-term impact on their development
Cyclin‐dependent kinase 13 is indispensable for normal mouse heart development
Get PDFCongenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin-dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13-related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X-gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT-qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high-resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13-related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD
One Year of Gluten-Free Diet Impacts Gut Function and Microbiome in Celiac Disease
Get PDFBackground & AimsCurrently, the main treatment for celiac disease (CD) is the gluten-free diet (GFD). This observational cohort study investigated the impact of CD and 1 year of GFD on gut function and microbiome.MethodsA total of 36 newly diagnosed patients and 36 healthy volunteers (HVs) were studied at baseline and at 12-month follow-up. Small bowel water content (SBWC), whole gut transit time (WGTT), and colon volumes were measured by magnetic resonance imaging. Stool sample DNA was subjected to shotgun metagenomic sequencing. Species-level abundances and gene functions, including CAZymes (carbohydrate active enzymes) were determined.ResultsSBWC was significantly higher in people with CD (157 ± 15 mL) vs (HVs 100 ± 12 mL) (P = .003). WGTT was delayed in people with CD (68 ± 8 hours) vs HVs (41 ± 5 hours) (P = .002). The differences reduced after 12 months of GFD but not significantly. Well-being in the CD group significantly improved after GFD but did not recover to control values. CD fecal microbiota showed a high abundance of proteolytic gene functions, associated with Escherichia coli, Enterobacter, and Peptostreptococcus. GFD significantly reduced Bifidobacteria and increased Blautia wexlerae. Microbiome composition correlated positively with WGTT, colonic volume, and Akkermansia municphilia but negatively with B wexerelae. Following GFD, the reduction in WGTT and colonic volume was significantly associated with increased abundance of B wexlerae. There were also significant alterations in CAZyme profiles, specifically starch- and arabinoxylan-degrading families.ConclusionsCD impacted gut function and microbiota. GFD ameliorated but did not reverse these effects, significantly reducing Bifidobacteria associated with reduced intake of resistant starch and arabinoxylan from wheat. ClinicalTrials.gov, number: NCT02551289
Tunnelling-induced wall damage: An appraisal of elastoplastic constitutive models for masonry
Get PDFThis paper investigates the role of masonry elastoplastic constitutive models on tunnelling-induced damage in buildings. A two-stage analysis method (TSAM) is adopted, incorporating input greenfield displacements, 3D masonry walls, and an elastic model for the soil. The paper focuses on four masonry constitutive models that can be readily adopted for routine analysis in industry. Comparison of in-plane yield surfaces with experimental data indicates that, among the considered masonry models, the Concrete Damaged Plasticity model under biaxial calibration gives the best overall performance. The TSAM is then used to study selected tunnel-masonry wall scenarios, confirming a significant effect of the constitutive model and its parameters on masonry wall response to tunnelling, particularly after volume losses where moderate damage is triggered. Also, as masonry stress paths are shown to concentrate in the tensile–compressive areas, with damage prediction being sensitive to the yield surface within this quadrant, numerical damage predictions must rely on the accurate calibration of the constitutive model in the tensile–compressive quadrants. This appraisal indicates that, in the context of routine structure modelling for tunnelling assessments, the selection of elastoplastic masonry models and their biaxial calibration have a non-negligible impact on the damage category estimate
The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain
Get PDFObjectivesHistological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.MethodsRats (n=8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery. Pain behaviour (weight bearing asymmetry and mechanical hindpaw withdrawal thresholds (PWTs)) were measured and knee samples obtained. Features associated with BMLs were evaluated using haematoxylin and eosin or Safranin-O stained knee sections. Sections were scored for chondropathy, osteophytes, synovitis and with the human OA Bone Score modified for rats (rOABS). rOABS reliability was assessed with intraclass correlation coefficient (ICC), groups were compared using Mann-Whitney U-tests, and associations examined with Spearman’s rho.ResultsOABS features were more prevalent in each OA pain group than in controls. rOABS displayed good inter-rater reliability (ICC=0.79). rOABS was higher in each model than controls; MIA 3.0 (2.3 to 4.0) vs vehicle 0.0 (0.0 to 0.0), and MNX 4.0 (2.3 to 4.8) vs sham 0.0 (0.0 to 0.0), each p<0.003. rOABS was associated with OA cartilage involvement (rho=0.69, p<0.001), osteophyte (rho=0.61, p<0.001) and synovial inflammation (rho=0.76, p<0.001). Higher rOABS was associated with pain behaviour: weight bearing asymmetry (rho=0.65, p<0.001) and PWT (rho=-0.47, p=0.003).ConclusionsSubchondral pathology in rat OA models resembles human subchondral BMLs. rOABS reliably measured subchondral pathology and was associated with OA structure and pain behaviour
Antenatal pelvic floor muscle exercise intervention led by midwives in England to reduce postnatal urinary incontinence: APPEAL feasibility and pilot randomised controlled cluster trial
Get PDFObjectives To assess the feasibility of an intervention of midwifery support for antenatal pelvic floor muscle exercises (PFME) to prevent postnatal urinary incontinence (UI). Design Feasibility and pilot cluster randomised controlled trial. Clusters were community midwifery teams. Setting Community maternity antenatal care. Participants One hundred seventy-five women; 186 midwives. Intervention Midwifery training and resources for midwives and women to support antenatal PFME. Control clusters continued standard care. Outcomes Women reporting: that their midwife explained how to do PFME, PFME adherence and postpartum UI. Midwives reporting: pre-post-training PFME confidence, intervention acceptability. Fidelity of training delivery and implementation. Results Ninety-five midwives in intervention clusters; 91 midwives in control clusters. Of 998 women sent questionnaires, 175 responded: 15.8% in intervention, 16.4% in control clusters. Women's characteristics in both trial arms were similar and characteristics of respondents and non-respondents were similar. Sixty-five percent (95% CI 56.9% to 72.4%) of women in intervention clusters reported their midwife explained how to do PFME vs 38% (95% CI 24.6% to 51.2%) in control clusters. Fifty percent (95% CI 24.1% to 77.1%) of women in intervention clusters vs 38% (95% CI 12.4% to 67.1%) in control clusters reported doing enough PFME to potentially prevent UI. Fourty-four percent (95% CI 32.0% to 56.1%) of women in intervention clusters reported UI vs 54% (95% CI 42.2% to 65.8%) in control clusters. Intervention training was delivered with fidelity and received positively. Midwives reported improvements in PFME confidence/knowledge (median increase of at least 1 point on a 0-4 scale for each of eight questions). Midwives (26%) most frequently reported insufficient time as an implementation barrier. Conclusions This pilot trial produced consistent new findings that training and resourcing midwives to teach and support pregnant women to undertake PFME is acceptable and feasible for women and midwives. It increased the number of women who are informed about PFME, with potential to improve PFME adherence and reduce postpartum UI. Recent changes to the National Health Service perinatal pelvic healthcare means a full trial is not possible
Double-quantum filtered 23Na NMR and MRI: Selective detection of ordered sodium in an inhomogeneous B0 field
Get PDFDouble-quantum filtered 23Na NMR experiments with one or two “magic angle” (54.7°) pulses in the filter step are widely used for selective observation of sodium ions that are interacting with ordered biological structures (“ordered sodium”) and hence exhibit a distribution of quadrupolar splittings in their NMR spectrum. This approach has recently been extended to 23Na MRI where the conventional experiment has been modified, omitting the 180° pulse to reduce the absorption of radiofrequency energy during human studies. Here, the “magic angle” double-quantum filtered 23Na NMR experiment (without a 180° pulse) is analysed in terms of coherence pathways that lead to refocusing in an inhomogeneous B0 field (“echoes”) and those that do not (“antiechoes”). It is shown that the echo and antiecho pathways can be separated by phase cycling and that the antiecho pathway contributes very little to the overall signal in an inhomogeneous B0 field. Hence, a double-quantum filtered 23Na NMR experiment that utilises just the echo pathway and so achieves complete refocusing of the effects of B0 inhomogeneity without making use of a 180° pulse is proposed. The new method is demonstrated both in 23Na NMR spectroscopy in an inhomogeneous B0 field and in 23Na MRI of a three-component phantom
Development and internal–external cross-validation of a patient-reported definition for acute calcium pyrophosphate crystal arthritis
Get PDFObjectiveTo develop and validate a patient-reported definition of acute calcium pyrophosphate (CPP) crystal arthritis in people with crystal-proven CPP deposition (CPPD) disease.MethodsConsecutive patients with crystal-proven CPPD disease from seven centres across four countries were enrolled in a cross-sectional study. In each centre, patient-reported outcomes on the features of acute CPP crystal arthritis were collected. The expert opinion of an independent rheumatologist was the reference standard. We developed definitions based on multivariable logistic regression model with backward selection of predictors and classification and regression tree (CART) approaches.ResultsTwo hundred and forty-six patients [mean age 73.2 years (s.d. 10.7), 65.9% female] were enrolled. At the time of the assessment, acute CPP crystal arthritis was diagnosed in 96/246 (39.0%) participants.Patient-reported joint warmth, patient-reported joint swelling, time from pain onset to peak, and self-reported acute CPP crystal inflammatory arthritis were included in the multivariable logistic model. This model had good discrimination (optimism-adjusted c-index: 0.92; 95% CI: 0.89, 0.95) and calibration (optimism-adjusted calibration slope: 0.95; 95% CI: 0.71, 1.19; optimism-adjusted calibration-in-the-large: 0.005; 95% CI: −0.37, 0.37) in the internal validation. Probability threshold ≥0.53 had sensitivity of 0.83 (95% CI: 0.74, 0.90) and specificity of 0.86 (95% CI: 0.79, 0.91). Performances were similar in the internal–external cross-validation. The CART identified patient-reported acute CPP crystal inflammatory arthritis, followed by joint swelling and joint warmth as the most informative variables for ascertaining acute CPP crystal arthritis [sensitivity 0.83 (95% CI: 0.72, 0.91) and specificity 0.83 (95% CI: 0.74, 0.90)].ConclusionWe developed and initially validated easy-to-use patient-reported definitions for acute CPP crystal arthritis for use in clinical trials and observational research in CPPD
Characterising the Concentration-Dependent Behaviour of Heat-Treated Sunflower Oleosomes at an Air-Water Interface
Get PDFThe behaviour of fresh and heat-treated sunflower oleosomes (oil bodies) at the air-water interface was studied using a force tensiometer with a conventional method and a new approach based on the fresh interface formation. Oleosomes were recovered using a wet milling process and washed to produce washed oil bodies (WOB), then dispersed as rinsed-washed oil bodies (RWOB) in ultra-pure water. Thermal treatment of oleosomes at 75 °C for 5 min did not alter the quality of oleosomes so it was used as the pasteurisation treatment. All oleosome preparations, including fresh RWOB, reduced surface tension (ST) at the air-water interface. Fresh RWOB exhibited faster, and more extensive ST reduction compared to heat-treated samples (HT-RWOB). Serum phase (a protein rich phase produced as part of the oleosome purification process) analysis indicated extraneous proteins contribute to ST reduction. ST measurements using HT-RWOB showed concentration-dependent ST reduction from 0.005% to 0.1% (w/v), with minimal changes at higher concentrations. Fitting a linear model on the concentration-dependent zone and concentration-independent zone showed that the cross over happens at the concentration of 0.1% (w/v) which is regarded as the critical packing concentration (CPC, the concentration by which the interface is saturated). Colloidal instability phenomena were observed at high concentrations. Particle size measurement and micrographs of emulsions before and after ST measurement indicate significant breakage and coalescence of oleosomes at high concentrations because of the formation of multiple layers at the interface after the CPC. This paper explores the impact of these changes on the ST and suggests possible explanations
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