Polymer Matrix Nanocomposites by Inkjet Printing

This paper describes work on a continuing project to form functional composites that contain ceramic nanoparticles using a Solid Freeform Fabrication (SFF) inkjet printing method. The process involves inkjet deposition of monomer/particle suspensions in layers followed by curing each layer in sequence using UV radiation. The reactive monomer is hexanediol-diacrylate (HDODA); the polymer forming reaction proceeds by a free radical mechanism. The liquid monomer containing nanoparticles is essentially a printing ink formulation. Successfully suspending the particles in the monomer is critical. We have developed a surface treatment method for forming stable suspensions of the nanoparticles so that they remain discrete throughout the processing sequence. The SFF process involves careful control of the polymer cure so that the interface between layers is seamless and residual stresses in the composites are eliminated. An immediate use for such composites is in optical applications as gradient refractive index lenses (GRIN). GRIN lenses have planar surfaces, eliminating the need for costly grinding and polishing. The planar surfaces also eliminate optical aberrations that result at the edges of spherical lenses and diminish the accuracy of focus. If the appropriate nanoparticles are fully dispersed they will modify the polymer's refractive index without interfering with light transmission. The effect is additive with volume concentration. Using 'inks' of different compositions in a multiple nozzle inkjet printer allows the formation of composites with precise composition gradients. Since an object is built one planar layer at a time, changes can be made readily both within each layer and from layer to layer. Inkjet printing with picoliter resolution is ideal for this task. Working with SiC nanoparticles in HDODA as a model system for demonstrating the inkjet deposition process, nanocomposite films with a linear concentration gradient varying from 0 to 4.5% (wt) were fabricated on Silicon wafers. These composites are 30 layer films, which total 140µm in thickness. Each layer in the composite is about 5 µm in thickness. Analytical methods for characterizing the dispersion of the nanoparticles in the composite and some of the salient optical properties of the composites also were established. The status of the program is reviewed in this paper.Mechanical Engineerin

Genetic dissection of essential hypertension and familial intracranial aneurysm

The studies of hypertension, described herein, combined complementary strategies to examine the relevance of human chromosome 5q31.1-qter to blood pressure as a quantitative trait, and hypertension as a qualitative trait. This distal region of chromosome 5 was focused upon due to its implication by other human and animal model studies and the cluster of cardiovascular candidate genes located there. Eleven microsatellites across 55 cM of 5q31.1 to qter were genotyped in 212 hypertensive nuclear families of the Silesian Hypertension Study. Two-point and multipoint analyses showed linkage of a 7 cM region to both hypertensive status and blood pressure phenotypes. A maximal multipoint Z-score of 2.2 for systolic blood pressure (SBP) was obtained proximal to the marker D5s1480. In light of the debate regarding significance in linkage studies, this quantitative trait locus (QTL) was confirmed in a second sample derived from the Scottish population. Genotyping of the same markers was done for 1,469 individuals from sibships of the MIDSPAN Family Study. Two-point and multipoint analyses confirmed a reproducible 7 cM QTL with a maximum multipoint logarithm of odds (LOD) score of 1.8 obtained for mean arterial pressure. Several putative candidate genes were located within the QTL including the b2-adrenergic receptor gene, ADRB2, which is known to have a major role in cardiovascular physiology. Three functional loci, Arg16Gly, Gln27Glu and Thr164Ile, were genotyped within the ADRB2 gene using the Silesian sample. Single locus and haplotype analyses using transmission disequilibrium tests and family-based association methods showed no association to hypertension status (P>0.05), effectively excluding this gene in the Silesian sample. The fibroblast growth factor 1 gene, FGF1, is located at the centre of the QTL. This gene had previously been cited as a putative blood pressure candidate gene in the 5q region but not studied in humans. With roles in endothelial cell proliferation, possible oxidative stress defence and proven direct effects on blood pressure in rodent models, we considered it a possible novel candidate. Coding regions and 3’ UTR were sequenced and family-based association analyses performed for three polymorphisms which were discovered in the 3’ UTR. Association of SBP (P=0.045), pulse pressure (P=0.019) and hypertension status (P=0.038) was demonstrated to the most proximal locus. Association of hypertension to a three-locus haplotype was also shown (P=0.020). The work on essential hypertension demonstrated the merit of confirming linkage in independent populations, implicating a 7 cM region of 5q31.1-q33 linked to blood pressure. Subsequent candidate gene studies utilised the added value of haplotype analyses, excluding the ADRB2 locus but showing interesting data to implicate the novel FGF1 locus as a putative positional candidate. Further fine mapping strategies are now underway to define, more clearly, the haplotype tag across the FGF1 locus

Anxious/depressed symptoms are related to microstructural maturation of white matter in typically developing youths

AbstractThere are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.</jats:p

Impact of the COVID-19 global pandemic on symptomatic diagnosis of cancer - the view from primary care

The entire landscape of cancer management in primary care, from case identification to the management of those living with and beyond cancer, is evolving rapidly in the face of the coronavirus (COVID-19) pandemic.1 In a climate of fear and mandated avoidance of all but essential clinical services, delays in patient, population and healthcare system responses to suspected cancer symptoms seem inevitable

Development of a behaviour change intervention to encourage timely cancer symptom presentation among people living in deprived communities using the Behaviour Change Wheel

We are grateful to the National Awareness and Early Diagnosis Initiative (NAEDI) for funding this work. The NAEDI funding consortium, under the auspices of the National Cancer Research Institute (NCRI), consists of Cancer Research UK; Department of Health (England); Economic and Social Research Council; Health and Social Care R&D Division, Public Health Agency (Northern Ireland); National Institute for Social Care and Health Research (Wales); and the Scottish Government. We would like to thank ABACus project management team members Tim Banks and Maura Matthews from Tenovus Cancer Care for their ongoing support and involvement in the project. The authors would also like to acknowledge the support of the ABACus steering group (Danny Antebi, Tracey Deacon, Karen Gully, Jane Hanson, Sharon Hillier, Alex Murray, Richard Neal, Gill Richardson, Mark Rogers, and Sara Thomas). Compliance with Ethical StandardsPeer reviewedPublisher PD

Martian magnetism with orbiting sub-millimeter sensor:simulated retrieval system

A Mars-orbiting sub-millimeter sensor can be used to retrieve the magnetic field at low altitudes over large areas of significant planetary crustal magnetism of the surface of Mars from measurements of circularly polarized radiation emitted by the 368 GHz ground-state molecular oxygen absorption line. We design a full retrieval system for one example orbit to show the expected accuracies on the magnetic field components that one realization of such a Mars satellite mission could achieve. For one set of measurements around a tangent profile, we find that the two horizontal components of the magnetic field can be measured at about 200 nT error with a vertical resolution of around 4 km from 6 up to 70 km in tangent altitude. The error is similar regardless of the true strength of the magnetic field, and it can be reduced by repeated measurements over the same area. The method and some of its potential pitfalls are described and discussed

Implementing Shared Decision Making in the NHS: Lessons from the MAGIC Programme

Contains fulltext : 174279.pdf (publisher's version ) (Open Access

Societal and equity challenges for Brain Health Services. A user manual for Brain Health Services-part 6 of 6.

Brain Health Services are a novel approach to the personalized prevention of dementia. In this paper, we consider how such services can best reflect their social, cultural, and economic context and, in doing so, deliver fair and equitable access to risk reduction. We present specific areas of challenge associated with the social context for dementia prevention. The first concentrates on how Brain Health Services engage with the "at-risk" individual, recognizing the range of factors that shape an individual's risk of dementia and the efficacy of risk reduction measures. The second emphasizes the social context of Brain Health Services themselves and their ability to provide equitable access to risk reduction. We then elaborate proposals for meeting or mitigating these challenges. We suggest that considering these challenges will enable Brain Health Services to address two fundamental questions: the balance between an individualized "high-risk" and population focus for public health prevention and the ability of services to meet ethical standards of justice and health equity

Porphyromonas gingivalis initiates a mesenchymal-like transition through ZEB1 in gingival epithelial cells

The oral anaerobe Porphyromonas gingivalis is associated with the development of cancers including oral squamous cell carcinoma (OSCC). Here we show that infection of gingival epithelial cells with P. gingivalis induces expression and nuclear localization of the ZEB1 transcription factor which controls epithelial-mesenchymal transition (EMT). P. gingivalis also caused an increase in ZEB1 expression as a dual species community with Fusobacterium nucleatum or Streptococcus gordonii. Increased ZEB1 expression was associated with elevated ZEB1 promoter activity and did not require suppression of the miR-200 family of micro RNAs. P. gingivalis strains lacking the FimA fimbrial protein were attenuated in their ability to induce ZEB1 expression. ZEB1 levels correlated with an increase in expression of mesenchymal markers, including vimentin and MMP-9, and with enhanced migration of epithelial cells into matrigel. Knockdown of ZEB1 with siRNA prevented the P. gingivalis-induced increase in mesenchymal markers and epithelial cell migration. Oral infection of mice by P. gingivalis increased ZEB1 levels in gingival tissues, and intracellular P. gingivalis were detected by antibody staining in biopsy samples from OSCC. These findings indicate that FimA-driven ZEB1 expression could provide a mechanistic basis for a P. gingivalis contribution to OSCC