Intraoperative contrast-enhanced sonography of bowel blood flow: preliminary experience

The potential to predict, and therefore avoid, anastomotic failure has eluded generations of colon and rectal surgeons to date. A reliable, reproducible method of assessing bowel blood flow therefore would be of enormous potential clinical relevance. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We present our study assessing the feasibility of using contrast-enhanced sonography to study bowel perfusion intraoperatively. We studied 8 patients (4 male and 4 female) with an age range of 52 to 81 years who underwent colorectal surgery (right hemicolectomies, n = 3; Hartmann procedure, n = 1; anterior resections, n = 2; and bowel resections with ileocolic anastomoses, n = 2). A 5-mL bolus of a sulfur hexafluoride contrast agent solution was injected before and after vascular ligation with simultaneous noncompression ultrasound scanning directly over the large bowel. The patients were followed clinically to assess for leaks. Contrast-enhanced sonographic time-intensity curves were generated for the time to peak and maximum amplitude. Moderate interobserver agreement was shown for the time to peak (κ = 0.50) and maximum amplitude (κ = 0.42), and moderate intraobserver agreement was shown for the time to peak (κ= 0.53) and maximum amplitude (κ= 0.53). No significant differences were shown between the time to peak (P = .28) and maximum amplitude (P = .49) for the preligation and postligation scans. To our knowledge, intraoperative contrast-enhanced sonography of the bowel has not been performed previously. We have shown the technique to be feasible with good intraobserver and interobserver agreement. Further work is ongoing to optimize the technique and assess its use in predicting anastomotic breakdown.published_or_final_versio

Solvation and surface effects on polymorph stabilities at the nanoscale

We explore the effects of particle size and solvent environment on the thermodynamic stability of two pairs of polymorphs subjected to ball-mill neat grinding (NG) and liquid assisted grinding (LAG). Two systems were studied: (i) forms I and II of a 1 : 1 theophylline : benzamide cocrystal and (ii) forms A and B of an aromatic disulfide compound. For both systems, the most stable-bulk polymorph converted to the metastable-bulk polymorph upon NG. LAG experiments yielded different outcomes depending on the amount of solvent used. This was further investigated by performing carefully controlled LAG experiments with increasing $\mu$L amounts of solvents of different nature. With these experiments, we were able to monitor form A to B and form I to II conversions as a function of solvent concentration and derive polymorph equilibrium curves. The concentration required for a switch in polymorphic outcome was found to be dependent on solvent nature. We propose that these experiments demonstrate a switch in thermodynamic stability of the polymorphs in the milling jar. Form B, the stable-bulk polymorph, has less stable surfaces than form A, thus becoming metastable at the nanoscale when surface effects become important. $\textit{Ex situ}$ diffraction and electron microscopy data confirm crystal sizes in the order of tens of nanometers after the ball mill grinding experiments reach equilibrium. DFT-d computations of the polymorph particles stabilities support these findings and were used to calculate cross-over sizes of forms A and B as a function of solvent. Attachment energies and surface stabilities of the various crystalline faces exposed were found to be very sensitive to the solvent environment. Our findings suggest that surface effects are significant in polymorphism at the nanoscale and that the outcomes of equilibrium ball-mill NG and LAG experiments are in general controlled by thermodynamics.Engineering and Physical Sciences Research Counci

Benchmarking 2D hydraulic models for urban flood simulations

This paper describes benchmark testing of six two-dimensional (2D) hydraulic models (DIVAST, DIVASTTVD, TUFLOW, JFLOW, TRENT and LISFLOOD-FP) in terms of their ability to simulate surface flows in a densely urbanised area. The models are applied to a 1·0 km × 0·4 km urban catchment within the city of Glasgow, Scotland, UK, and are used to simulate a flood event that occurred at this site on 30 July 2002. An identical numerical grid describing the underlying topography is constructed for each model, using a combination of airborne laser altimetry (LiDAR) fused with digital map data, and used to run a benchmark simulation. Two numerical experiments were then conducted to test the response of each model to topographic error and uncertainty over friction parameterisation. While all the models tested produce plausible results, subtle differences between particular groups of codes give considerable insight into both the practice and science of urban hydraulic modelling. In particular, the results show that the terrain data available from modern LiDAR systems are sufficiently accurate and resolved for simulating urban flows, but such data need to be fused with digital map data of building topology and land use to gain maximum benefit from the information contained therein. When such terrain data are available, uncertainty in friction parameters becomes a more dominant factor than topographic error for typical problems. The simulations also show that flows in urban environments are characterised by numerous transitions to supercritical flow and numerical shocks. However, the effects of these are localised and they do not appear to affect overall wave propagation. In contrast, inertia terms are shown to be important in this particular case, but the specific characteristics of the test site may mean that this does not hold more generally

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Amniotic fluid volume: Rapid MR-based assessment at 28-32 weeks gestation.

OBJECTIVES: This work evaluates rapid magnetic resonance projection hydrography (PH) based amniotic fluid volume (AFV) estimates against established routine ultrasound single deepest vertical pocket (SDVP) and amniotic fluid index (AFI) measurements, in utero at 28-32 weeks gestation. Manual multi-section planimetry (MSP) based measurement of AFV is used as a proxy reference standard. METHODS: Thirty-five women with a healthy singleton pregnancy (20-41 years) attending routine antenatal ultrasound were recruited. SDVP and AFI were measured using ultrasound, with same day MRI assessing AFV with PH and MSP. The relationships between the respective techniques were assessed using linear regression analysis and Bland-Altman method comparison statistics. RESULTS: When comparing estimated AFV, a highly significant relationship was observed between PH and the reference standard MSP (R(2) = 0.802, p < 0.001). For the US measurements, SDVP measurement related most closely to amniotic fluid volume, (R(2) = 0.470, p < 0.001), with AFI demonstrating a weaker relationship (R(2) = 0.208, p = 0.007). CONCLUSION: This study shows that rapid MRI based PH measurement is a better predictor of AFV, relating more closely to our proxy standard than established US techniques. Although larger validation studies across a range of gestational ages are required this approach could form part of MR fetal assessment, particularly where poly- or oligohydramnios is suspected. KEY POINTS: • MR projection hydrography can be used to estimate amniotic fluid volume. • MR projection hydrography relies on the T2w signal from amniotic fluid. • Amniotic fluid volume (AFV) is more accurately assessed than with ultrasound.This study was supported by the National Institute of Health Research, Cambridge Biomedical Research Centre. The authors also acknowledge the support of Addenbrooke’s Charitable Trust and thank the participants for their contribution to the study.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00330-015-4179-

Health research improves healthcare: now we have the evidence and the chance to help the WHO spread such benefits globally

There has been a dramatic increase in the body of evidence demonstrating the benefits that come from health research. In 2014, the funding bodies for higher education in the UK conducted an assessment of research using an approach termed the Research Excellence Framework (REF). As one element of the REF, universities and medical schools in the UK submitted 1,621 case studies claiming to show the impact of their health and other life sciences research conducted over the last 20 years. The recently published results show many case studies were judged positively as providing examples of the wide range and extensive nature of the benefits from such research, including the development of new treatments and screening programmes that resulted in considerable reductions in mortality and morbidity. Analysis of specific case studies yet again illustrates the international dimension of progress in health research; however, as has also long been argued, not all populations fully share the benefits. In recognition of this, in May 2013 the World Health Assembly requested the World Health Organization (WHO) to establish a Global Observatory on Health Research and Development (R&D) as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilise resources to address diseases that disproportionately affect the world’s poorest countries. As editors of Health Research Policy and Systems (HARPS), we are delighted that our journal has been invited to help inform the establishment of the WHO Global Observatory through a Call for Papers covering a range of topics relevant to the Observatory, including topics on which HARPS has published articles over the last few months, such as approaches to assessing research results, measuring expenditure data with a focus on R&D, and landscape analyses of platforms for implementing R&D. Topics related to research capacity building may also be considered. The task of establishing a Global Observatory on Health R&D to achieve the specified objectives will not be easy; nevertheless, this Call for Papers is well timed – it comes just at the point where the evidence of the benefits from health research has been considerably strengthened

A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii

Peer reviewedPublisher PD

Lack of phenotypic and evolutionary cross-resistance against parasitoids and pathogens in Drosophila melanogaster

BackgroundWhen organisms are attacked by multiple natural enemies, the evolution of a resistance mechanism to one natural enemy will be influenced by the degree of cross-resistance to another natural enemy. Cross-resistance can be positive, when a resistance mechanism against one natural enemy also offers resistance to another; or negative, in the form of a trade-off, when an increase in resistance against one natural enemy results in a decrease in resistance against another. Using Drosophila melanogaster, an important model system for the evolution of invertebrate immunity, we test for the existence of cross-resistance against parasites and pathogens, at both a phenotypic and evolutionary level.MethodsWe used a field strain of D. melanogaster to test whether surviving parasitism by the parasitoid Asobara tabida has an effect on the resistance against Beauveria bassiana, an entomopathogenic fungus; and whether infection with the microsporidian Tubulinosema kingi has an effect on the resistance against A. tabida. We used lines selected for increased resistance to A. tabida to test whether increased parasitoid resistance has an effect on resistance against B. bassiana and T. kingi. We used lines selected for increased tolerance against B. bassiana to test whether increased fungal resistance has an effect on resistance against A. tabida.Results/ConclusionsWe found no positive cross-resistance or trade-offs in the resistance to parasites and pathogens. This is an important finding, given the use of D. melanogaster as a model system for the evolution of invertebrate immunity. The lack of any cross-resistance to parasites and pathogens, at both the phenotypic and the evolutionary level, suggests that evolution of resistance against one class of natural enemies is largely independent of evolution of resistance against the other

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media

Otitis media ( OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM