X-ray diffraction from bone employing annular and semi-annular beams

This is the final version of the article. Available from the publisher via the DOI in this record.There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.We acknowledge gratefully the funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC) grant number EP/K020196/

Broken symmetry states and divergent resistance in suspended bilayer graphene

Graphene [1] and its bilayer have generated tremendous excitement in the physics community due to their unique electronic properties [2]. The intrinsic physics of these materials, however, is partially masked by disorder, which can arise from various sources such as ripples [3] or charged impurities [4]. Recent improvements in quality have been achieved by suspending graphene flakes [5,6], yielding samples with very high mobilities and little charge inhomogeneity. Here we report the fabrication of suspended bilayer graphene devices with very little disorder. We observe fully developed quantized Hall states at magnetic fields of 0.2 T, as well as broken symmetry states at intermediate filling factors $\nu = 0$, $\pm 1$, $\pm 2$ and $\pm 3$. The devices exhibit extremely high resistance in the $\nu = 0$ state that grows with magnetic field and scales as magnetic field divided by temperature. This resistance is predominantly affected by the perpendicular component of the applied field, indicating that the broken symmetry states arise from many-body interactions.Comment: 23 pages, including 4 figures and supplementary information; accepted to Nature Physic

Fresh water influence on nutrient stoichiometry in a tropical estuary, southwest coast of India

Cochin backwaters, a micro tidal estuary, undergo a characteristic transformation from a river-dominated system during summer monsoon to a tide-dominant system during pre-monsoon season. The present study observes that as the river flow weakens after monsoon, the flushing of the estuary diminishes and the nitrogen and phosphorous loadings through anthropogenic activities (industries) and sediment re-suspension alter the nutrient stoichiometry substantially. The increased tidal activity during pre-monsoon changes the estuary into a vertically mixed, eutrophic and flow-restricted system supporting an enhanced organic production. This implies that monsoon-induced hydrology plays an important role in regulating the nutrients, secondary production and even the migrant fauna of the estuary. The system is delicately poised, as continuous release of pollutants including nutrients into this estuary would suppress fish and shell fish production, where only pollution tolerant species can exist

Survey of ultrasound practice amongst podiatrists in the UK

Background: Ultrasound in podiatry practice encompasses musculoskeletal ultrasound imaging, vascular hand-held Doppler ultrasound and therapeutic ultrasound. Sonography practice is not regulated by the Health and Care Professions Council (HCPC), with no requirement to hold a formal qualification. The College of Podiatry does not currently define ultrasound training and competencies. This study aimed to determine the current use of ultrasound, training received and mentorship received and/or provided by podiatrists using ultrasound. Methods: A quantitative study utilising a cross-sectional, on-line, single-event survey was undertaken within the UK. Results: Completed surveys were received from 284 podiatrists; 173 (70%) use ultrasound as part of their general practice, 139 (49%) for musculoskeletal problems, 131 (46%) for vascular assessment and 39 (14%) to support their surgical practice. Almost a quarter (n=62) worked for more than one organisation; 202 (71%) were employed by the NHS and/or private sector (n=118, 41%). Nearly all (93%) respondents report using a hand-held vascular Doppler in their daily practice; 216 (82%) to support decisions regarding treatment options, 102 (39%) to provide diagnostic reports for other health professionals, and 34 (13%) to guide nerve blocks. Ultrasound imaging was used by 104 (37%) respondents primarily to aid clinical decision making (n=81) and guide interventions (steroid injections n=67; nerve blocks n=39). Ninety-three percent stated they use ultrasound imaging to treat their own patients, while others scan at the request of other podiatrists (n=28) or health professionals (n=18). Few use ultrasound imaging for research (n=7) or education (n=2). Only 32 (11%) respondents (n=20 private sector) use therapeutic ultrasound to treat patients presenting with musculoskeletal complaints, namely tendon pathologies. Few respondents (18%) had completed formal post-graduate CASE (Consortium for the Accreditation of Sonographic Education) accredited ultrasound courses. Forty (14%) respondents receive ultrasound mentorship; the majority from fellow podiatrists (n=17) or medical colleagues (n=15). Over half (n=127) who do not have ultrasound mentorship indicated they would like a mentor predominantly for ultrasound imaging. Fifty-five (19%) report they currently provide ultrasound mentorship for others. Conclusions: Understanding the scope of ultrasound practice, the training undertaken and the requirements for mentorship will underpin the development of competencies and recommendations defined by the College of Podiatry to support professional development and ensure safe practice.</p

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

Infrared emission towards SN 1987A 11 years after outburst: Measurements with ISOCAM

We present measurements of the mid-infrared (MIR) emission from SN 1987A, made using the Infrared Space Observatory (ISO) 11 years after outburst. They are the only late epoch detections of this source in the thermal IR regime. The position of the source, determined from an offset to an IR-emitting star, suggests that the emission is associated with SN 1987A or its extended supernova remnant (SNR). A predominantly circumstellar origin is however suggested by the size and orientation of the IR-emitting region, which is comparable with the extension of the inner ring seen with the Hubble Space Telescope (HST). The emission is most probably from collisionally-heated circumstellar grains embedded in shocked gas downstream of the blast wave. The MIR extent is consistent with the hypothesis that the blast wave was propagating into material of moderate density interior to the thick inner ring at the epoch of the ISOCAM observations

The non-Abelian gauge theory of matrix big bangs

We study at the classical and quantum mechanical level the time-dependent Yang-Mills theory that one obtains via the generalisation of discrete light-cone quantisation to singular homogeneous plane waves. The non-Abelian nature of this theory is known to be important for physics near the singularity, at least as far as the number of degrees of freedom is concerned. We will show that the quartic interaction is always subleading as one approaches the singularity and that close enough to t=0 the evolution is driven by the diverging tachyonic mass term. The evolution towards asymptotically flat space-time also reveals some surprising features.Comment: 29 pages, 8 eps figures, v2: minor changes, references added: v3 small typographical changes

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

EM-mosaic detects mosaic point mutations that contribute to congenital heart disease.

BackgroundThe contribution of somatic mosaicism, or genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined.MethodsWe developed a new computational method, EM-mosaic (Expectation-Maximization-based detection of mosaicism), to analyze mosaicism in exome sequences derived primarily from blood DNA of 2530 CHD proband-parent trios. To optimize this method, we measured mosaic detection power as a function of sequencing depth. In parallel, we analyzed our cohort using MosaicHunter, a Bayesian genotyping algorithm-based mosaic detection tool, and compared the two methods. The accuracy of these mosaic variant detection algorithms was assessed using an independent resequencing method. We then applied both methods to detect mosaicism in cardiac tissue-derived exome sequences of 66 participants for which matched blood and heart tissue was available.ResultsEM-mosaic detected 326 mosaic mutations in blood and/or cardiac tissue DNA. Of the 309 detected in blood DNA, 85/97 (88%) tested were independently confirmed, while 7/17 (41%) candidates of 17 detected in cardiac tissue were confirmed. MosaicHunter detected an additional 64 mosaics, of which 23/46 (50%) among 58 candidates from blood and 4/6 (67%) of 6 candidates from cardiac tissue confirmed. Twenty-five mosaic variants altered CHD-risk genes, affecting 1% of our cohort. Of these 25, 22/22 candidates tested were confirmed. Variants predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The estimated true frequency of mosaic variants above 10% mosaicism was 0.14/person in blood and 0.21/person in cardiac tissue. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction.ConclusionsWe estimate that ~ 1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses