Liquid-liquid equilibrium in polymer-fullerene mixtures; an in situ neutron reflectivity study.

The composition profiles of a series of model polystyrene/fullerene bilayers are measured, before, during and after thermal annealing, using in situ neutron reflectometry. In combination with grazing-incidence X-ray diffraction measurements, these experiments, which quantify layer compositions as a function of molecular weight using changes in both scattering length density and layer thickness, extend and corroborate recent measurements on ex situ annealed samples and demonstrate that the composition profiles rapidly formed in these systems correspond to two co-existing liquid-liquid phases in thermodynamic equilibrium. The measurements also demonstrate a clear and systematic onset temperature for diffusion of the fullerenes into the PS layer that correlates with the known glass-transition temperatures of both the polymer (as a function of molecular weight) and the fullerene, revealing that the molecular mobility of the fullerenes in these systems is controlled by the intrinsic mobility of the fullerenes themselves and the ability of the polymer to plasticise the fullerenes at the interface. Over the temperature range investigated (up to 145 °C), measurements of equilibrated composition profiles as a function of temperature (during gradual cooling) reveal no significant changes in composition profile, other than those associated with the known thermal expansion/contraction of polystyrene thin-films.

Analysis of genetic variation contributing to measured speed in Thoroughbreds identifies genomic regions involved in the transcriptional response to exercise.

Despite strong selection for athletic traits in Thoroughbred horses, there is marked variation in speed and aptitude for racing performance within the breed. Using global positioning system monitoring during exercise training, we measured speed variables and temporal changes in speed with age to derive phenotypes for GWAS. The aim of the study was to test the hypothesis that genetic variation contributes to variation in end-point physiological traits, in this case galloping speed measured during field exercise tests. Standardisation of field-measured phenotypes was attempted by assessing horses exercised on the same gallop track and managed under similar conditions by a single trainer. PCA of six key speed indices captured 73.9% of the variation with principal component 1 (PC1). Verifying the utility of the phenotype, we observed that PC1 (median) in 2-year-old horses was significantly different among elite, non-elite and unraced horses (P < 0.001) and the temporal change with age in PC1 varied among horses with different myostatin (MSTN) g.66493737C>T SNP genotypes. A GWAS for PC1 in 2-year-old horses (n = 122) identified four SNPs reaching the suggestive threshold for association (P < 4.80 × 10-5 ), defining a 1.09 Mb candidate region on ECA8 containing the myosin XVIIIB (MYO18B) gene. In a GWAS for temporal change in PC1 with age (n = 168), five SNPs reached the suggestive threshold for association and defined candidate regions on ECA2 and ECA11. Both regions contained genes that are significantly differentially expressed in equine skeletal muscle in response to acute exercise and training stimuli, including MYO18A. As MYO18A plays a regulatory role in the skeletal muscle response to exercise, the identified genomic variation proximal to the myosin family genes may be important for the regulation of the response to exercise and training.

A genomic prediction model for racecourse starts in the Thoroughbred horse.

Durability traits in Thoroughbred horses are heritable, economically valuable and may affect horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2  = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced horses (16% unraced) than did low (27% unraced) potential horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict horses with a greater chance of a racecourse start.

The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions.

BACKGROUND: Race distance aptitude in Thoroughbred horses is highly heritable and is influenced largely by variation at the myostatin gene (MSTN). OBJECTIVES: In addition to MSTN, we hypothesised that other modifying loci contribute to best race distance. STUDY DESIGN: Using 3006 Thoroughbreds, including 835 'elite' horses, which were >3 years old, had race records and were sampled from Europe/Middle-East, Australia/New Zealand, North America and South Africa, we performed genome-wide association (GWA) tests and separately developed a genomic prediction algorithm to comprehensively catalogue additive genetic variation contributing to best race distance. METHODS: 48,896 single-nucleotide polymorphism (SNP) genotypes were generated from high-density SNP genotyping arrays. Heritability estimates, tests of GWA and genomic prediction models were derived for the phenotypes: average race distance, best race distance for elite, nonelite and all winning horses. RESULTS: Heritability estimates were high ( h m 2  = 0.51, best race distance - elite; h m 2  = 0.42, best race distance - nonelite; h m 2  = 0.40, best race distance - all) and most of the variation was attributed to the MSTN gene. MSTN locus SNPs were the most strongly associated with the trait and included BIEC2-438999 (ECA18:66913090; P = 4.51 × 10-110 , average race distance; P = 2.33 × 10-42 , best race distance - elite). The genomic prediction algorithm enabled the inclusion of variation from all SNPs in a model that partitioned horses into short and long cohorts following assignment of MSTN genotype. Additional genes with minor contributions to best race distance were identified. MAIN LIMITATIONS: The nongenetic influence of owner/trainer decisions on placement of horses in suitable races could not be controlled. CONCLUSIONS: MSTN is the single most important genetic contributor to best race distance in the Thoroughbred. Employment of genetic prediction models will lead to more accurate placing of horses in races that are best suited to their inherited genetic potential for distance aptitude.

High sensitivity organic inorganic hybrid X-ray detectors with direct transduction and broadband response.

X-ray detectors are critical to healthcare diagnostics, cancer therapy and homeland security, with many potential uses limited by system cost and/or detector dimensions. Current X-ray detector sensitivities are limited by the bulk X-ray attenuation of the materials and consequently necessitate thick crystals (~1 mm-1 cm), resulting in rigid structures, high operational voltages and high cost. Here we present a disruptive, flexible, low cost, broadband, and high sensitivity direct X-ray transduction technology produced by embedding high atomic number bismuth oxide nanoparticles in an organic bulk heterojunction. These hybrid detectors demonstrate sensitivities of 1712 µC mGy-1 cm-3 for "soft" X-rays and ~30 and 58 µC mGy-1 cm-3 under 6 and 15 MV "hard" X-rays generated from a medical linear accelerator; strongly competing with the current solid state detectors, all achieved at low bias voltages (-10 V) and low power, enabling detector operation powered by coin cell batteries.

Corrigendum: Palaeo leaf economics reveal a shift in ecosystem function associated with the end-Triassic mass extinction event.

This corrects the article DOI: 10.1038/nplants.2017.104.

Palaeo leaf economics reveal a shift in ecosystem function associated with the end-Triassic mass extinction event.

Climate change is likely to have altered the ecological functioning of past ecosystems, and is likely to alter functioning in the future; however, the magnitude and direction of such changes are difficult to predict. Here we use a deep-time case study to evaluate the impact of a well-constrained CO2-induced global warming event on the ecological functioning of dominant plant communities. We use leaf mass per area (LMA), a widely used trait in modern plant ecology, to infer the palaeoecological strategy of fossil plant taxa. We show that palaeo-LMA can be inferred from fossil leaf cuticles based on a tight relationship between LMA and cuticle thickness observed among extant gymnosperms. Application of this new palaeo-LMA proxy to fossil gymnosperms from East Greenland reveals significant shifts in the dominant ecological strategies of vegetation found across the Triassic-Jurassic transition. Late Triassic forests, dominated by low-LMA taxa with inferred high transpiration rates and short leaf lifespans, were replaced in the Early Jurassic by forests dominated by high-LMA taxa that were likely to have slower metabolic rates. We suggest that extreme CO2-induced global warming selected for taxa with high LMA associated with a stress-tolerant strategy and that adaptive plasticity in leaf functional traits such as LMA contributed to post-warming ecological success.

Increased non-melanoma skin cancer risk in young patients with inflammatory bowel disease on immunomodulatory therapy: a retrospective single-centre cohort study.

BACKGROUND: Recent studies report an increased risk of non-melanoma skin cancer (NMSC) in immunosuppressed patients with inflammatory bowel disease (IBD). Concurrently, paediatric IBD incidence is rising, with more patients now exposed to immunomodulators from a younger age. OBJECTIVES: To investigate NMSC incidence and to examine the risk associated with immunomodulators in the development of NMSC in patients with IBD. METHODS: This was a retrospective single-centre cohort study. Patients with IBD attending a tertiary adult hospital from 1994 to 2013 were included. Skin cancer incidence was compared with population data from the National Cancer Registry of Ireland (NCRI) to calculate standardized incidence ratio (SIR). Logistic regression was utilized for risk factor analysis. RESULTS: Two thousand and fifty-three patients with IBD were studied. The SIR for NMSC in patients with IBD taking immunomodulators overall was 1.8 (95% CI: 1.0-2.7) with age-specific rates significantly elevated across certain age categories. Exposure to thiopurines (OR: 5.26, 95% CI: 2.15-12.93, P < 0.001) and in particular thiopurines and/or tumour necrosis factor alpha (TNF-α) inhibitors (OR: 6.45, 95% CI: 2.69-15.95, P < 0.001) was significantly associated with NMSC. The majority (82%) of those exposed to a TNF-α inhibitor also had thiopurine exposure. CONCLUSIONS: Compliance with skin cancer preventative measures should be highlighted to all patients with IBD. There should be a low threshold for dermatology referral for immunosuppressed patients, particularly those with a history of exposure to dual immunomodulators from a young age.

Porosity of silica Stöber particles determined by spin-echo small angle neutron scattering.

Stöber silica particles are used in a diverse range of applications. Despite their widespread industrial and scientific uses, information on the internal structure of the particles is non-trivial to obtain and is not often reported. In this work we have used spin-echo small angle neutron scattering (SESANS) in conjunction with ultra small angle X-ray scattering (USAXS) and pycnometry to study an aqueous dispersion of Stöber particles. Our results are in agreement with models which propose that Stöber particles have a porous core, with a significant fraction of the pores inaccessible to solvent. For samples prepared from the same master sample in a range of H2O : D2O ratio solutions we were able to model the SESANS results for the solution series assuming monodisperse, smooth surfaced spheres of radius 83 nm with an internal open pore volume fraction of 32% and a closed pore fraction of 10%. Our results are consistent with USAXS measurements. The protocol developed and discussed here shows that the SESANS technique is a powerful way to investigate particles much larger than those studied using conventional small angle scattering methods.

Interaction of partially denatured insulin with a DSPC floating lipid bilayer.

The carefully controlled permeability of cellular membranes to biological molecules is key to life. In degenerative diseases associated with protein misfolding and aggregation, protein molecules or their aggregates are believed to permeate these barriers and threaten membrane integrity. We used neutron reflectivity to study the interaction of insulin, a model amyloidogenic protein, with a DSPC floating lipid bilayer. Structural changes consistent with protein partitioning to the membrane interior and adsorption to a gel phase model lipid bilayer were observed under conditions where the native fold of the protein is significantly destabilised. We propose that the perturbation of the membrane by misfolded proteins involves long term occupation of the membrane by these proteins, rather than transient perforation events.

Spin echo small angle neutron scattering using a continuously pumped (3)He neutron polarisation analyser.

We present a new instrument for spin echo small angle neutron scattering (SESANS) developed at the Low Energy Neutron Source at Indiana University. A description of the various instrument components is given along with the performance of these components. At the heart of the instrument are a series of resistive coils to encode the neutron trajectory into the neutron polarisation. These are shown to work well over a broad range of neutron wavelengths. Neutron polarisation analysis is accomplished using a continuously operating neutron spin filter polarised by Rb spin-exchange optical pumping of (3)He. We describe the performance of the analyser along with a study of the (3)He polarisation stability and its implications for SESANS measurements. Scattering from silica Stöber particles is investigated and agrees with samples run on similar instruments.

A solution concentration dependent transition from self-stratification to lateral phase separation in spin-cast PS:d-PMMA thin films.

Thin films with a rich variety of different nano-scale morphologies have been produced by spin casting solutions of various concentrations of PS:d-PMMA blends from toluene solutions. During the spin casting process specular reflectivity and off-specular scattering data were recorded and ex situ optical and atomic force microscopy, neutron reflectivity and ellipsometry have all been used to characterise the film morphologies. We show that it is possible to selectively control the film morphology by altering the solution concentration used. Low polymer concentration solutions favour the formation of flat in-plane phase-separated bi-layers, with a d-PMMA-rich layer underneath a PS-rich layer. At intermediate concentrations the films formed consist of an in-plane phase-separated bi-layer with an undulating interface and also have some secondary phase-separated pockets rich in d-PMMA in the PS-rich layer and vice versa. Using high concentration solutions results in laterally phase-separated regions with sharp interfaces. As with the intermediate concentrations, secondary phase separation was also observed, especially at the top surface.

High transvalvular pressure gradients on intraoperative transesophageal echocardiography after aortic valve replacement: what does it mean?

Intraoperative transesophageal echocardiography is now used routinely during aortic valve replacement, allowing immediate evaluation of replaced or repaired valves. It is well recognised that high transvalvular pressure gradients can be detected immediately after implantation of a prosthetic aortic valve which may be due to multifactorial confounding variables, including functional phenomena, pressure recovery and prosthesis-patient mismatch. This review article explores the variety of methods available for assessing prosthetic aortic valve function and considers causative factors which may contribute to high transvalvular gradients in an attempt to determine whether a physical problem with the valve exists, or whether the valve is functioning normally.

The efficiency of encapsulation within surface rehydrated polymersomes.

The key to the use of polymersomes as effective molecular delivery systems is in the ability to design processing routes that can efficiently encapsulate the molecular payload. We have evaluated various surface rehydration mechanisms for encapsulation, in each case characterizing the morphologies formed using DLS and confocal microscopy as well as determining the encapsulation efficiency for the hydrophilic dye Rhodamine B. In contrast to bulk methods, where the encapsulation efficiencies are low, we find that higher efficiencies can be obtained by the rehydration of thin films. We relate these results to the non-equilibrium mechanisms that underlie vesicle formation and discuss how an understanding of these mechanisms can help optimize encapsulation efficiencies. Our conclusion is that, even considering the good encapsulation efficiency, surface methods are still unsuitable for the massive scale-up needed when applied to commercial "mass market" molecular delivery scenarios. However, targeting more specialized applications for high value ingredients (like pharmaceuticals) might be more feasible.

The diagnosis and classification of inguinal and femoral hernia on multisection spiral CT.

AIM: To assess the contribution of high-quality multiplanar reconstructions of the groin from multisection computed tomography (CT) to the accurate diagnosis of inguinal and femoral hernias. MATERIALS AND METHODS: Twenty-eight patients who had undergone both a contrast-enhanced CT and a herniorrhaphy were identified from hospital records. Seventeen were excluded, as the images did not include the groin area. The remaining 11 images were re evaluated on a workstation without knowledge of the surgical findings and the hernias were identified and classified using the axial data and coronal and sagittal reconstructions. Anatomical structures and radiological details that hindered or aided this classification were recorded. RESULTS: Hernias were identified in nine out of the 11 patients. Of the seven inguinal hernias, six were identified with the correct side recorded in each case. Of the four patients with surgical data that distinguished direct from indirect inguinal hernias, the correct diagnosis was provided in all cases using CT. Of the four patients with a femoral hernia CT was used to correctly classify three. Among the three available planes, the axial was particularly poor for the identification of the inguinal ligament compared with the other planes. In contrast, the coronal views were very useful in the evaluation of femoral hernias. CONCLUSIONS: The high-resolution coronal and sagittal images available from multisection CT now permit the accurate diagnosis of groin hernias. Using simple anatomical criteria, direct and indirect inguinal hernias and femoral hernias can be reliably distinguished, abolishing the need for surrogate markers, which was hitherto necessary.

Radiologic anatomy of the inguinofemoral region: insights from MDCT.

OBJECTIVE: We set out to reexamine the radiologic anatomy of the inguinofemoral region using volume data sets obtained with an MDCT scanner. MATERIALS AND METHODS: We conducted a systematic prospective review of CT scans of 20 consecutively enrolled patients, 10 men and 10 women chosen retrospectively from our CT database. An experienced radiologist and a senior trainee surgeon conducted an image review to maximize recognition of relevant anatomic detail. RESULTS: The inferior epigastric artery and femoral canal were identified in all planes in all patients. On axial views a spur on the pubic bone was visible in 17 (85%) of the patients, but the inguinal ligament was not reliably identified in any. The round ligament or spermatic cord was visible in only 15 (75%) of 20 patients. In contrast, on coronal and sagittal views, the inguinal ligament, which is vital to reliable identification and accurate classification of groin hernias, was visible in 19 (95%) of the 20 patients. Scans in the sagittal plane best depicted the gutter-like aspect of the ligament, the canal and contents being clearly visible in 95% of the patients. On sagittal views, the internal ring was identifiable in 90% and the round ligament or spermatic cord in 95% of the patients. On coronal images, the internal ring was identified in all and the conjoint tendon in 95% of the patients. The round ligament or spermatic cord was not seen in 10% of the patients. CONCLUSION: MDCT produces images of the inguinal region in detail not possible with previous generations of scanners. In our small series, 100% identification of key anatomic structures was achieved when information from all three views was combined. We found subtle differences between imaging findings and standard anatomic teaching.

Responsive brushes and gels as components of soft nanotechnology.

Progress in the development of generic molecular devices based on responsive polymers is discussed. Characterisation of specially synthesised polyelectrolyte gels, "grafted from" brushes and triblock copolymers is reported. A Landolt pH-oscillator, based on bromate/ sulfite/ferrocyanide, with a room temperature period of 20 min and a range of 3.1 < pH < 7.0, has been used to drive periodic oscillations in volume in a pH responsive hydrogel. The gel is coupled to the reaction and changes volume by a factor of at least 6. A continuously stirred, constant volume, tank reactor was set-up on an optical microscope and the reaction pH and gel size monitored. The cyclic force generation of this system has been measured directly in a modified JKR experiment. The responsive nature of polyelectrolyte brushes, grown by surface initiated ATRP, have been characterised by scanning force microscopy, neutron reflectometry and single molecule force measurements. Triblock copolymers, based on hydrophobic end-blocks and either polyacid or polybase mid-block, have been used to produce polymer gels where the deformation of the molecules can be followed directly by SAXS and a correlation between molecular shape change and macroscopic deformation has been established. The three systems studied allow both the macroscopic and a molecular response to be investigated independently for the crosslinked gels and the brushes. The triblock copolymers demonstrate that the individual response of the polyelectrolyte molecules scale-up to give the macroscopic response of the system in an oscillating chemical reaction.