Honeycomb sterna: an unusual case of a developmental abnormality in the sternum

This report details an unusual case of a human sternal developmental abnormality of an anatomical specimen part of the skeletal collection curated by University College London, Anthropology Department skeletal collection. This rarely reported developmental abnormality is caused by the non-fusion of lateral ossification centres in the sternebrae, resulting in the mesosternum having a honeycomb-like appearance. Sternal defects are typically underreported in the clinical literature as many cases being asymptomatic that they are typically diagnosed incidentally, as such there is a dearth in our current understanding of the development and anatomical variants of the sternum. Although in recent years, large-scale CT studies have investigated the prevalence of sternal developmental abnormalities, these studies have not reported sternal defects similar to the individual presented in this report. While most sternal defects are clinically uneventful, the lack of awareness of these variants can result in misinterpretation of radiological and pathological findings as such an understanding of anatomical variants even when asymptomatic is vital

Cryptotephra as a dating and correlation tool in archaeology

A new development in archaeological chronology involves the use of far travelled volcanic ash which may form discrete but invisible layers within a site's stratigraphy. Known as cryptotephra, these horizons can provide isochrons for the precise correlation of archaeological records at single moments in time, removing, or at least significantly reducing, temporal uncertainty within inter-site comparisons. When a tephra can be dated elsewhere, its age can be imported between records, providing an independent check on other dating methods in use and valuable age estimates for difficult to date sequences. The use of cryptotephra layers to date and correlate palaeoenvironmental archives is well established and there exists a wealth of tephra compositional data and regional tephrostratigraphic frameworks from which archaeological cryptotephra studies can benefit greatly. Existing approaches to finding and analysing cryptotephra are easily adapted to archaeological sequences, so long as the often complex nature of archaeological stratigraphies and sediment taphonomy are borne in mind. © 2013 Elsevier Ltd

Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.

BACKGROUND: Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. METHODS: The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. FINDINGS: Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4-3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk [RR] 1·60, 95% CI 1·22-2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction=0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9-8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2-34·0, p<0·0001). INTERPRETATION: Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. FUNDING: National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare.This work was supported by the National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre and the Stillbirth and Neonatal Death Society. DP was supported by a Medical Research Council (MRC) Clinical Training Fellowship. IRW is supported by a MRC Unit Programme (number U105260558). GE Healthcare (Fairfield, CT, USA) donated two Voluson i ultrasound systems for this study. This study was also supported by the NIHR Cambridge Clinical Research Facility, where all visits at about 20, 28, and 36 weeks took place. No direct or indirectly supporting bodies for the project were involved in any aspect of preparation of this paper for publication. We thank the Perinatal Institute for providing a bulk calculator for customised percentiles of estimated fetal weight. We thank all the women who participated in the study, and all the staff in the Rosie Hospital (Cambridge, UK) and NIHR Cambridge Clinical Research Facility who provided direct or indirect assistance for the study.This is the final published version of the article. It was originally published in The Lancet (Sovio U, White IR, Dacey A, Pasupathy D, Smith GCS, The Lancet, 2015, doi:10.1016/S0140-6736(15)00131-2). The final version is available at http://dx.doi.org/10.1016/S0140-6736(15)00131-2

Positron kinetics in an idealized PET environment

The kinetic theory of non-relativistic positrons in an idealized positron emission tomography PET environment is developed by solving the Boltzmann equation, allowing for coherent and incoherent elastic, inelastic, ionizing and annihilating collisions through positronium formation. An analytic expression is obtained for the positronium formation rate, as a function of distance from a spherical source, in terms of the solutions of the general kinetic eigenvalue problem. Numerical estimates of the positron range - a fundamental limitation on the accuracy of PET, are given for positrons in a model of liquid water, a surrogate for human tissue. Comparisons are made with the 'gas-phase' assumption used in current models in which coherent scattering is suppressed. Our results show that this assumption leads to an error of the order of a factor of approximately 2, emphasizing the need to accurately account for the structure of the medium in PET simulations

Correcting for optimistic prediction in small data sets.

The C statistic is a commonly reported measure of screening test performance. Optimistic estimation of the C statistic is a frequent problem because of overfitting of statistical models in small data sets, and methods exist to correct for this issue. However, many studies do not use such methods, and those that do correct for optimism use diverse methods, some of which are known to be biased. We used clinical data sets (United Kingdom Down syndrome screening data from Glasgow (1991-2003), Edinburgh (1999-2003), and Cambridge (1990-2006), as well as Scottish national pregnancy discharge data (2004-2007)) to evaluate different approaches to adjustment for optimism. We found that sample splitting, cross-validation without replication, and leave-1-out cross-validation produced optimism-adjusted estimates of the C statistic that were biased and/or associated with greater absolute error than other available methods. Cross-validation with replication, bootstrapping, and a new method (leave-pair-out cross-validation) all generated unbiased optimism-adjusted estimates of the C statistic and had similar absolute errors in the clinical data set. Larger simulation studies confirmed that all 3 methods performed similarly with 10 or more events per variable, or when the C statistic was 0.9 or greater. However, with lower events per variable or lower C statistics, bootstrapping tended to be optimistic but with lower absolute and mean squared errors than both methods of cross-validation

Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study.

BACKGROUND: There have been dramatic changes in the approach to screening for aneuploidy over the last 20 years. However, the approach to screening for other complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth remains largely unchanged. Randomised controlled trials of routine application of high tech screening methods to the general population have generally failed to show improvement in outcome. We have previously reviewed this and concluded it was due, in large part, to poor performance of screening tests. Here, we report a study design where the primary aim is to generate clinically useful methods to screen women to assess their risk of adverse pregnancy outcome. METHODS/DESIGN: We report the design of a prospective cohort study of unselected primiparous women recruited at the time of their first ultrasound scan. Participation involves serial phlebotomy and obstetric ultrasound at the dating ultrasound scan (typically 10-14 weeks), 20 weeks, 28 weeks and 36 weeks gestation. In addition, maternal demographic details are obtained; maternal and paternal height are measured and maternal weight is serially measured during the pregnancy; maternal, paternal and offspring DNA are collected; and, samples of placenta and membranes are collected at birth. Data will be analysed as a prospective cohort study, a case-cohort study, and a nested case-control study. DISCUSSION: The study is expected to provide a resource for the identification of novel biomarkers for adverse pregnancy outcome and to evaluate the performance of biomarkers and serial ultrasonography in providing clinically useful prediction of risk

Norbornene chaotropic salts as low molecular mass ionic organogelators (LMIOGs)

Phenylalanine functionalised norbornene (9:Na) functions as a potent, low molecular-mass (MW = 333 Da) ionic organogelator with a minimum gelating concentration of 0.5 wt% in THF, i-PrOH, 1,4-dioxane and n-BuOH. Fibrous crystals form in the gel and X-ray crystallography identified a cation mediated helical assembly process controlled by the chirality of the phenylalanine. In additon to excellent gelating properties 9:Na readily forms aqueous biphasic and triphasic systems

Conductivity of Strongly Coupled Striped Superconductor

We study the conductivity of a strongly coupled striped superconductor using gauge/gravity duality (holography). The study is done analytically, in the large modulation regime. We show that the optical conductivity is inhomogeneous but isotropic at low temperatures. Near but below the critical temperature, we calculate the conductivity analytically at small frequency \omega, and find it to be both inhomogeneous and anisotropic. The anisotropy is imaginary and scales like 1/\omega. We also calculate analytically the speed of the second sound and the thermodynamic susceptibility.Comment: 32 page

MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer

Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients