Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation.

OBJECTIVE: To evaluate a soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio cut-off of 38 for the prediction of pre-eclampsia (PE) in routine assessment in singleton pregnancies at 30-37 weeks' gestation. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan at 30-37 weeks as part of routine pregnancy care. Serum sFlt-1 and PlGF were measured and their ratio was calculated. We estimated the detection rate (DR), false-positive rate (FPR), positive predictive value (PPV) and negative predictive value (NPV) of sFlt-1/PlGF ratio >38 for the prediction of delivery with PE at < 1, < 4 and ≥ 4 weeks after assessment. RESULTS: The study population of 12 305 singleton pregnancies was examined at a median of 32.4 (range, 30.0-36.9) weeks and included 14 (0.11%), 77 (0.63%) and 227 (1.84%) cases that subsequently delivered with PE at < 1, < 4 or ≥ 4 weeks' after assessment, respectively. The DR, FPR, PPV and NPV of sFlt-1/PlGF ratio > 38 in the prediction of delivery with PE at < 1 week were 78.6%, 4.5%, 1.9% and 99.97%, respectively; the values for delivery with PE at < 4 weeks were 76.6%, 4.1%, 10.4% and 99.85% and for delivery with PE ≥ 4 weeks were 20.7%, 4.3%, 8.3% and 98.47%. CONCLUSION: In routine screening of singleton pregnancies, the performance of a sFlt-1/PlGF ratio > 38 is modest for the prediction of delivery with PE at < 1 and at < 4 weeks after assessment and poor for the prediction of delivery with PE at ≥ 4 weeks after assessment. A sFlt-1/PlGF ratio > 38 predicted 79% of cases delivering with PE at < 1 week after assessment, at a FPR of 4.5%; consequently, a policy of hospitalizing patients with a ratio > 38 would potentially lead to unnecessary hospitalization in 4.5% of pregnancies and a ratio of ≤ 38 would falsely reassure one fifth of women who will deliver with PE within 1 week of assessment. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Microfluidically fabricated pH-responsive anionic amphiphilic microgels for drug release.

Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic acid (AA) and the hydrophobic, non-ionic n-butyl acrylate (BuA) were synthesised using a lab-on-a-chip device. Hydrophobic droplets were generated via a microfluidic platform that contained a protected form of AA, BuA, the hydrophobic crosslinker, ethylene glycol dimethacrylate (EGDMA), and a free radical initiator in an organic solvent. These hydrophobic droplets were photopolymerised within the microfluidic channels and subsequently hydrolysed, enabling an integrated platform for the rapid, automated, and in situ production of anionic amphiphilic microgels. The amphiphilic microgels did not feature the conventional core-shell structure but were instead based on random amphiphilic copolymers of AA and BuA and hydrophobic crosslinks. Due to their amphiphilic nature they were able to encapsulate and deliver both hydrophobic and hydrophilic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the surrounding aqueous solution and the hydrophobic content of the microgels.

Tailoring pH-responsive acrylic acid microgels with hydrophobic crosslinks for drug release.

Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of different compositions were synthesised using a lab-on-a-chip device. The microgels were formed by polymerising hydrophobic droplets. The droplets were generated via a microfluidic platform and contained a protected form of AA, a hydrophobic crosslinker (ethylene glycol dimethacrylate, EGDMA) and a free radical initiator in an organic solvent. Following photopolymerisation and subsequent hydrolysis, AA based microgels of amphiphilic nature were produced and it was demonstrated that they can successfully deliver both hydrophilic as well as hydrophobic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the aqueous solution as well as the crosslinking density and hydrophobic content of the microgels.

Heterostructures produced from nanosheet-based inks.

The new paradigm of heterostructures based on two-dimensional (2D) atomic crystals has already led to the observation of exciting physical phenomena and creation of novel devices. The possibility of combining layers of different 2D materials in one stack allows unprecedented control over the electronic and optical properties of the resulting material. Still, the current method of mechanical transfer of individual 2D crystals, though allowing exceptional control over the quality of such structures and interfaces, is not scalable. Here we show that such heterostructures can be assembled from chemically exfoliated 2D crystals, allowing for low-cost and scalable methods to be used in device fabrication.

Electronic properties of graphene encapsulated with different two-dimensional atomic crystals.

Hexagonal boron nitride is the only substrate that has so far allowed graphene devices exhibiting micrometer-scale ballistic transport. Can other atomically flat crystals be used as substrates for making quality graphene heterostructures? Here we report on our search for alternative substrates. The devices fabricated by encapsulating graphene with molybdenum or tungsten disulfides and hBN are found to exhibit consistently high carrier mobilities of about 60 000 cm(2) V(-1) s(-1). In contrast, encapsulation with atomically flat layered oxides such as mica, bismuth strontium calcium copper oxide, and vanadium pentoxide results in exceptionally low quality of graphene devices with mobilities of ∼1000 cm(2) V(-1) s(-1). We attribute the difference mainly to self-cleansing that takes place at interfaces between graphene, hBN, and transition metal dichalcogenides. Surface contamination assembles into large pockets allowing the rest of the interface to become atomically clean. The cleansing process does not occur for graphene on atomically flat oxide substrates.

Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatitis B surface antigen treated with rituximab.

Hepatitis B virus (HBV) can still be found within the hepatocytes after its clearance and the control of viral replication depends on the immune response. However during immunosuppression, seroconversion of HBsAg has been described followed by disease reactivation. Hepatitis B virus reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents and in particular, by the use of rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. We describe a case of a 64-year old female patient with rheumatoid arthritis and resolved HBV infection, who experienced a severe hepatitis B reactivation after the administration of rituximab.

Measurement of filling-factor-dependent magnetophonon resonances in graphene using Raman spectroscopy.

We perform polarization-resolved Raman spectroscopy on graphene in magnetic fields up to 45 T. This reveals a filling-factor-dependent, multicomponent anticrossing structure of the Raman G peak, resulting from magnetophonon resonances between magnetoexcitons and E(2g) phonons. This is explained with a model of Raman scattering taking into account the effects of spatially inhomogeneous carrier densities and strain. Random fluctuations of strain-induced pseudomagnetic fields lead to increased scattering intensity inside the anticrossing gap, consistent with the experiments.

Strong light-matter interactions in heterostructures of atomically thin films.

The isolation of various two-dimensional (2D) materials, and the possibility to combine them in vertical stacks, has created a new paradigm in materials science: heterostructures based on 2D crystals. Such a concept has already proven fruitful for a number of electronic applications in the area of ultrathin and flexible devices. Here, we expand the range of such structures to photoactive ones by using semiconducting transition metal dichalcogenides (TMDCs)/graphene stacks. Van Hove singularities in the electronic density of states of TMDC guarantees enhanced light-matter interactions, leading to enhanced photon absorption and electron-hole creation (which are collected in transparent graphene electrodes). This allows development of extremely efficient flexible photovoltaic devices with photoresponsivity above 0.1 ampere per watt (corresponding to an external quantum efficiency of above 30%).

Field-effect tunneling transistor based on vertical graphene heterostructures.

An obstacle to the use of graphene as an alternative to silicon electronics has been the absence of an energy gap between its conduction and valence bands, which makes it difficult to achieve low power dissipation in the OFF state. We report a bipolar field-effect transistor that exploits the low density of states in graphene and its one-atomic-layer thickness. Our prototype devices are graphene heterostructures with atomically thin boron nitride or molybdenum disulfide acting as a vertical transport barrier. They exhibit room-temperature switching ratios of ≈50 and ≈10,000, respectively. Such devices have potential for high-frequency operation and large-scale integration.

Crystal structure of human prion protein bound to a therapeutic antibody.

Prion infection is characterized by the conversion of host cellular prion protein (PrP(C)) into disease-related conformers (PrP(Sc)) and can be arrested in vivo by passive immunization with anti-PrP monoclonal antibodies. Here, we show that the ability of an antibody to cure prion-infected cells correlates with its binding affinity for PrP(C) rather than PrP(Sc). We have visualized this interaction at the molecular level by determining the crystal structure of human PrP bound to the Fab fragment of monoclonal antibody ICSM 18, which has the highest affinity for PrP(C) and the highest therapeutic potency in vitro and in vivo. In this crystal structure, human PrP is observed in its native PrP(C) conformation. Interactions between neighboring PrP molecules in the crystal structure are mediated by close homotypic contacts between residues at position 129 that lead to the formation of a 4-strand intermolecular beta-sheet. The importance of this residue in mediating protein-protein contact could explain the genetic susceptibility and prion strain selection determined by polymorphic residue 129 in human prion disease, one of the strongest common susceptibility polymorphisms known in any human disease.

Analysis of nitroxide spin label motion in a protein-protein complex using multiple frequency EPR spectroscopy.

X- and W-band EPR spectra, at room and low temperatures, are reported for nitroxide spin labels attached to cysteine residues selectively introduced into two proteins, the DNase domain of colicin-E9 and its immunity protein, Im9. The dynamics of each site of attachment on the individual proteins and in the tight DNase-Im9 complex have been analysed by computer simulations of the spectra using a model of Brownian dynamics trajectories for the spin label and protein. Ordering potentials have been introduced to describe mobility of labels restricted by the protein domain. Label mobility varies with position from completely immobilised, to motionally restricted and to freely rotating. Bi-modal dynamics of the spin label have been observed for several sites. We show that W-band spectra are particularly useful for detection of anisotropy of spin label motion. On complex formation significant changes are observed in the dynamics of labels at the binding interface region. This work reveals multi-frequency EPR as a sensitive and valuable tool for detecting conformational changes in protein structure and dynamics especially in protein-protein complexes.

Four novel mutations in patients from the Middle East with the infantile form of GM1-gangliosidosis.

GM1-gangliosidosis is a lysosomal storage disorder caused by a deficiency of beta-galactosidase. It is mainly characterized by progressive neurodegeneration and in its most severe infantile form it leads to death before the age of four. We have performed molecular analysis of five patients with the infantile form of GM1-gangliosidosis originating from the Middle East (two from Saudi Arabia and three from the United Arab Emirates). We have identified four novel mutations and one previously reported mutation in the GLB1 gene. The first novel mutation found in the homoallelic state in a patient from Saudi Arabia, is a c.171C>G transversion in exon 2 which creates a premature stop codon. Northern blot analysis in fibroblasts from the patient showed no mRNA and expression studies in COS-1 cells showed complete absence of the 85kDa precursor protein and no catalytic activity. The second novel mutation is a splicing error in intron 2, c.245+1G>A. This mutation was found in the heteroallelic state in a patient from Saudi Arabia, the second mutation being the previously described c.145C>T mutation. The third novel mutation is a missense mutation in exon 4, c.451G>T, found in the homoallelic state in a patient from the United Arab Emirates. Expression studies of this mutation in COS-1 cells showed complete absence of the 85kDa precursor protein and no catalytic activity. The fourth novel mutation is a splicing mutation in intron 8, c.914+4A>G, found in the homoallelic state in two siblings from the United Arab Emirates. This study has revealed genetic heterogeneity of the beta-galactosidase deficiency in the Arabic population [corrected]

Binding of sodium dodecyl sulfate to linear and star homopolymers of the nonionic poly(methoxyhexa(ethylene glycol) methacrylate) and the polycation poly(2-(dimethylamino)ethyl methacrylate): electromotive force, isothermal titration calorimetry, surface tension, and small-angle neutron scattering measurements.

We investigated the binding of sodium dodecyl sulfate (SDS) to various linear and star polymers of the nonionic methoxyhexa(ethylene glycol) methacrylate (PMHEGMA) and the ionic 2-(dimethylamino)ethyl methacrylate (PDMAEMA), the latter being a polycation at low pH. The dodecyl sulfate ion selective electrode (EMF), isothermal titration calorimetry (ITC), and surface tension (ST) were applied to gain detailed information about interactions. In all cases there is evidence of significant binding of SDS over an extensive SDS concentration range spanning from ca. 10(-6) to 0.1 mol dm(-3). At pH 3, the polymer PDMAEMA is a strong polycation and here the binding is dominated by electrostatic 1:1 charge neutralization with the anionic surfactant. At their natural pH of 8.6, PMHEGMA and PDMAEMA polymers are essentially nonionic and bind SDS in the form of polymer-bound aggregates in the concentration range of ca. 1 x 10(-3) to 3 x 10(-2) mol dm(-3). All the polymers also bind SDS to a lesser extent at concentrations below 1 x 10(-3) mol dm(-3) reaching as low as 10(-7) mol dm(-3). This low concentration binding process involves the polymer and nonassociated SDS monomers. As far as we are aware, this is the first example that such a low concentration noncooperative binding process could be observed in SDS/neutral polymer systems by EMF and ST. We also showed that the nonionic surfactant hexa(ethylene glycol) mono-n-dodecyl ether (C12EO6) and the cationic cetyltrimethylammonium bromide (C16TAB) interact with star PDMAEMA. We believe that the interaction of C12EO6 and CTAB is of similar noncooperative type as the first SDS binding process in the range from ca. 10(-5) to 0.3 x 10(-3) mol dm(-3). At the high concentration binding limit Csat of SDS, the above polymers become fully saturated with bound SDS micelles. We applied small angle neutron scattering (SANS) to determine the structure and aggregation numbers of the star polymer/bound SDS micelles and calculated the stoichiometry of such supramolecular complexes. The SANS data on PDMAEMA star polymers in the presence of C12EO6 showed only a limited monomer binding in contrast to linear PDMAEMA, which showed monomer C12EO6 binding at low concentrations but micellar aggregates at 6 x 10(-3) mol dm(-3).

Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients.

PURPOSE: To investigate the influence of ethnic origin on the incidence of keratoconus and the association of atopic diseases in patients with keratoconus. METHODS: Retrospective study of new patients referred to Dewsbury District General Hospital and diagnosed with keratoconus in a 6-year period between 1994 and 2000. The ethnic origin of the patient was defined as white, Asian, or other. Incidence was calculated from the catchment population of 176 774 (82% white people, 17% Asians, 1% others). t-Test, confidence intervals and chi2 tests were used to show statistical significance. RESULTS: A total of 74 cases of keratoconus were diagnosed over this period. Of these patients 29 (39%) were white and 45 (61%) were Asian. This equated to an incidence of keratoconus of 25 per 100 000 (1 in 4000) per year for Asians, compared with 3.3 per 100 000 (1 in 30 000) per year for white people (P<0.001). Asians presented significantly younger than white patients. The incidence of atopic disease was found to be significantly higher in white compared to Asian keratoconic patients. CONCLUSIONS: Asians were significantly more likely to present with keratoconus. The Asian patients were mostly of Northern Pakistani origin. This community has a tradition of consanguineous, especially first-cousin marriages. The higher incidence in this population was highly suggestive of a genetic factor being significant in the aetiology. The incidence was higher than revealed by previous studies. Atopic disease was significantly less common in Asians compared to white people, supporting the theory of a different aetiology in these patients.

Prevalence of systemic diseases in Brisbane general and periodontal practice patients.

BACKGROUND: Periodontitis has been associated with a number of systemic diseases such as atherosclerosis, coronary heart diseases, and respiratory diseases. This study aimed to determine whether there is a significant difference in the prevalence of systemic diseases (a) in patients referred for periodontal care compared to the general practice population, (b) in patients attending a public hospital and private practices, (c) in patients attending public and private periodontal practices, and (d) among patients with periodontitis of varying severity. METHODS: Charts of 1000 adult patients were selected from four clinics (University of Queensland (UQ) School of Dentistry Admissions Clinic, UQ School of Dentistry Periodontics Clinic, Private Periodontal Practice, and Private General Dental Practice). The prevalence of medical conditions was evaluated using validated self-reported health questionnaires. The periodontal condition was assessed from the most recent relevant radiographs in the files. RESULTS: Periodontal patients had a higher prevalence of systemic diseases compared to the general practice population. Public patients had a greater prevalence of systemic diseases compared to patients in private practice for both general practice and periodontal patients. In patients with advanced periodontitis, bronchitis, hepatitis and rheumatoid arthritis were most prevalent. Patients with periodontitis also took more medications and were more likely to suffer from multiple conditions compared to the general dental population. CONCLUSIONS: Patients attending public dental facilities have an increased prevalence of systemic disease compared to those attending private practices. Furthermore periodontal patients have a greater prevalence of diseases compared to general practice patients. Patients with moderate or advanced periodontitis show an increase in the prevalence of some systemic diseases previously reported to be risk factors for periodontal disease.