Rapid and mask-less laser-processing technique for the fabrication of microstructures in polydimethylsiloxane

We report a rapid laser-based method for structuring polydimethylsiloxane (PDMS) on the micron-scale. This mask-less method uses a digital multi-mirror device as a spatial light modulator to produce a given spatial intensity pattern to create arbitrarily shaped structures via either ablation or multi-photon photo-polymerisation in a master substrate, which is subsequently used to cast the complementary patterns in PDMS. This patterned PDMS mould was then used for micro-contact printing of ink and biological molecules

Depth resolution of Piezoresponse force microscopy

Given that a ferroelectric domain is generally a three dimensional entity, the determination of its area as well as its depth is mandatory for full characterization. Piezoresponse force microscopy (PFM) is known for its ability to map the lateral dimensions of ferroelectric domains with high accuracy. However, no depth profile information has been readily available so far. Here, we have used ferroelectric domains of known depth profile to determine the dependence of the PFM response on the depth of the domain, and thus effectively the depth resolution of PFM detection

Gravitational Geons in 1+1 Dimensions

It is well known that general relativity does not admit gravitational geons that are stationary, asymptotically flat, singularity free and topologically trivial. However, it is likely that general relativity will receive corrections at large curvatures and the modified field equations may admit solutions corresponding to this type of geon. If geons are produced in the early universe and survive until today they could account for some of the dark matter that has been "observed" in galaxies and galactic clusters. In this paper I consider gravitational geons in 1+1 dimensional theories of gravity. I show that the Jackiw-Teitelboim theory with corrections proportional to $R^2$ and $\Box R$ admits gravitational geons. I also show that gravitational geons exist in a class of theories that includes Lagrangians proportional to $R^{2/3}$.Comment: 8 pages, a comment added, two references corrected, to appear in Classical and Quantum Gravit

Investing in animal health research to alleviate poverty

This presentation starts with a discussion on the need of this study and outlines its framework. It then assesses in detail how to attack poverty, and tries to answer the question where do livestock and their diseases fit in? Then it presents the study design and how it is achieved. It then presents a quantitative assessment of poverty, and looks into qualitative approach, poverty indicators, livestock production systems, priority species for the poor along with their objectives and step to achieving them. It then presents an assessment of disease impact with examples. It then examines the distribution of poverty, the association of livestock species with the poor, animal diseases and their impact on the poor, and zoonotic diseases and their impact on the poor. It also presents in detail disease impact ranking. The role of research in alleviating poverty through animal health; research opportunities for the development and adaptation of disease control technologies targeted at the poor and for their delivery adoption and impact; the balance between diseases with the highest impact and the opportunities for research on their better control (a synthesis of research priorities) are other topics of discussion. The paper concludes its discussion with examining issues like generic areas from the field, generic delivery and adoption issues, synthesis of opportunities derived from all sources, and the balance between diseases with the highest impact and the opportunities for research on their better control. The presentation ends with a summary of funding requirements and sources

Precision nanoscale domain engineering of lithium niobate via UV laser induced inhibition of poling

Continuous wave ultraviolet (UV) laser irradiation at lambda=244 nm on the +z face of undoped and MgO doped congruent lithium niobate single crystals has been observed to inhibit ferroelectric domain inversion. The inhibition occurs directly beneath the illuminated regions, in a depth greater than 100 nm during subsequent electric field poling of the crystal. Domain inhibition was confirmed by both differential domain etching and piezoresponse force microscopy. This effect allows the formation of arbitrarily shaped domains in lithium niobate and forms the basis of a high spatial resolution micro-structuring approach when followed by chemical etching

Nanofabrication technologies: high-throughput for tomorrow's metadevices

Fabrication fundamentals1. Serial versus parallel? Most are currently fabricated by serial writing….2. Additive or subtractive?3. Feature size required.4. One-off demonstration (journal paper) or volume production (in the shops by next Christmas…)5. What material?6. Cost….(+ normalise to 150mm diameter wafer)7. Time to fabricat

Choosing the target difference ('effect size') for a randomised controlled trial - DELTA(2) guidance protocol

BACKGROUND: A key step in the design of a randomised controlled trial (RCT) is the estimation of the number of participants needed. By far the most common approach is to specify a target difference and then estimate the corresponding sample size; this sample size is chosen to provide reassurance that the trial will have high statistical power to detect such a difference between the randomised groups (at the planned statistical significance level). The sample size has many implications for the conduct of the study, as well as carrying scientific and ethical aspects to its choice. Despite the critical role of the target difference for the primary outcome in the design of an RCT, the manner in which it is determined has received little attention. This article reports the protocol of the Difference ELicitation in TriAls (DELTA(2)) project, which will produce guidance on the specification and reporting of the target difference for the primary outcome in a sample size calculation for RCTs. METHODS/DESIGN: The DELTA(2) project has five components: systematic literature reviews of recent methodological developments (stage 1) and existing funder guidance (stage 2); a Delphi study (stage 3); a 2-day consensus meeting bringing together researchers, funders and patient representatives, as well as one-off engagement sessions at relevant stakeholder meetings (stage 4); and the preparation and dissemination of a guidance document (stage 5). DISCUSSION: Specification of the target difference for the primary outcome is a key component of the design of an RCT. There is a need for better guidance for researchers and funders regarding specification and reporting of this aspect of trial design. The aim of this project is to produce consensus based guidance for researchers and funders

Anti-tumour necrosis factor therapy for Dupuytren's Disease: a randomised dose response proof of concept phase 2a clinical trial

Background Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor. Methods Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2). Secondary outcomes included levels of α-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings We recruited 28 patients, 8 assigned to the 15 mg, 12 to the 35 mg and 8 to the 40 mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of α-SMA protein expression in patients treated with 40 mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub group treated with 40 mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation In this dose-ranging study, injection of 40 mg of adalimumab in 0.4 ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytren's disease