Laser pulse control of a Q-switched Nd:YVO₄ bounce geometry laser using a secondary cavity

Pulsed laser operation is desirable for a wide range of applications such as laser micromachining in industrial manufacturing and laser marking for product identification. In these cases it is beneficial to have flexibility in the parameters of the laser pulse to suit the specific application. This can include the ability to achieve a wide range of pulse repetition rates, with some applications requiring variation of laser pulse rate from high rate (multi-kHz) to low rate or even an off-state in a fast timescale. To generate ultrahigh pulse rates requires Q-switched lasers with ultrahigh gain, but problems can arise if the modulation element is insufficient to prevent laser action or hold-off lasing at low repetition rates. In these cases, lasing output can occur when it is not desired. In this work we present a novel method for pulse control in a high gain bounce amplifier Q-switched system by using a secondary cavity to clamp the gain and allow for clean single pulse operation from very high (800kHz) to very low (e.g.1kHz) repetition rates

Efficient conversion to radial polarization in the two-micron band using a continuously space-variant half-waveplate

We demonstrate efficient conversion of a linearly-polarized Gaussian beam to a radially-polarised doughnut beam in the two-micron band using a continuously space-variant half-waveplate created by femtosecond writing of subwavelength gratings. The low scattering loss (<0.07) of this device indicates that it would be suitable for use with high power lasers

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain

From Stock Bottle to Vaccine: Elucidating the Particle Size Distributions of Aluminum Adjuvants Using Dynamic Light Scattering.

The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>9 μm) and Alhydrogel® exhibited the smallest median size (2677 ± 120 nm) in comparison to Adju-Phos® or Imject alum® (7152 ± 308 and 7294 ± 146 nm respectively) despite its large polydispersity index (PDI). Dilution of these materials induced some degree of disaggregation within all samples with Adju-Phos® being the most significantly affected. The presence of BSA caused the median size of Alhydrogel® to increase but these trends were not evident when model vaccines were formulated with either Adju-Phos® or Imject alum®. Nevertheless, Alhydrogel® and Adju-Phos® exhibited comparable median sizes in the presence of this protein (4194 ± 466 and 4850 ± 501 nm respectively) with Imject alum® being considerably smaller (2155 ± 485 nm). These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site

A profile of UK doctoral candidates in social work and social care

One important indication of the strength of a discipline is the state of its doctoral research. An important milestone for the official recognition of social work in the UK has been its inclusion in Economic and Social Research Council (ESRC) doctoral funding schemes. The current study assesses the longer-term impact of these schemes, via a 2013 survey, following up a previous one in 2008. A web-based survey of social work doctoral candidates in the UK (n = 216) was conducted, to profile student demographics, research topics, methods, challenges of and supports for doctoral work. Most doctoral candidates (70 per cent) were using a primarily qualitative research strategy and only 4 per cent were using a primarily quantitative approach. Social work doctoral candidates were slightly less satisfied with their research degree programme than the general population of doctoral students. Key areas of similarity with the 2008 survey included the demographical profile (gender, age, ethnicity) and the percentage who were qualified social workers; key differences included increased percentages of candidates who were registered full time, funded by the ESRC and doing a Ph.D., as opposed to a professional doctorate. The findings highlight a need for capacity building in quantitative research methods and improved support for this academic community

Unsung heroes: who supports social work students on placement?

Since the introduction of the three year degree programme in 2003, social work education has undergone a number of significant changes. The time students spend on placement has been increased to two hundred days, and the range of placement opportunities and the way in which these placements have been configured has significantly diversified. A consistent feature over the years, however, has been the presence of a Practice Educator (PE) who has guided, assessed and taught the student whilst on placement. Unsurprisingly, the role of the PE and the pivotal relationship they have with the student has been explored in the past and features in social work literature. This paper, however, concentrates on a range of other relationships which are of significance in providing support to students on placement. In particular it draws on research to discuss the role of the university contact tutor, the place of the wider team in which the student is sited, and the support offered by family, friends and others. Placements and the work undertaken by PE’s will continue to be integral to the delivery of social work education. It is, however, essential to recognise and value the often over looked role of others in providing support to students on placement

A Perturbation Theory for Ergodic Markov Chains and Application to Numerical Approximations

Perturbations to Markov chains and Markov processes are considered. The unperturbed problem is assumed to be geometrically ergodic in the sense usually established through the use of Foster--Lyapunov drift conditions. The perturbations are assumed to be uniform, in a weak sense, on bounded time intervals. The long-time behavior of the perturbed chain is studied. Applications are given to numerical approximations of a randomly impulsed ODE, an Itô stochastic differential equation (SDE), and a parabolic stochastic partial differential equation (SPDE) subject to space-time Brownian noise. Existing perturbation theories for geometrically ergodic Markov chains are not readily applicable to these situations since they require very stringent hypotheses on the perturbations

What Next After Metformin in Type 2 Diabetes? Selecting the Right Drug for the Right Patient

This is the final version. Available on open access from Springer via the DOI in this recordIntroduction: Metformin is the recommended initial treatment in type 2 diabetes mellitus (T2DM), but when this does not give adequate glucose control the choice of which second-line drug to use is uncertain as none have been found to have a better overall glycaemic response. In this real-world study dipeptidyl peptidase 4 inhibitors (DPP4i), sulphonylureas (SU), thiazolidinediones (TZD) and sodium glucose co-transporter 2 inhibitors (SGLT2i) were compared for their effectiveness in lowering glycated haemoglobin (HbA1c) levels for a particular individual based on their clinical characteristics. Methods: A retrospective analysis was undertaken of electronic health records of people with T2DM prescribed metformin alongside a DPP4i, SU, TZD or SGLT2i at second-line. Regression modelling was used to model the changes in HbA1c from baseline at month 6 and month 12 for the individual therapies, adjusting for demographic and clinical characteristics. Results: There were 7170 people included in the study. Treatment at second-line with SUs, DPP4i, TZDs and SGLT2i resulted in similar percentages of people achieving the recommended HbA1c target of < 7.5% (58 mmol/mol) at both 6 and 12 months. For those receiving SGLT2i and SUs, the greatest improvement in HbA1c was observed in relatively younger and older people, respectively. Trends were detected between other baseline characteristics and HbA1c improvement by drug class, but they were not statistically significant. Non-adherence rates were low for all drug classes. People with a higher medication possession ratio (≥ 80%) also had greater improvements in HbA1c at 12 months. Conclusion: This study identified patients’ phenotypic characteristics that may have the potential to influence individual treatment response. Accounting for these characteristics in clinical treatment decisions may facilitate individualised prescribing by being able to select the right drug for the right patient.Takeda UK Ltd

Mathematical modelling of adjuvant-enhanced active ingredient leaf uptake of pesticides

The global importance of effective and affordable pesticides to optimise crop yield and to support health of our growing population cannot be understated. But to develop new products or refine existing ones in response to climate and environmental changes is both time-intensive and expensive which is why the agrochemical industry is increasingly interested in using mechanistic models as part of their formulation development toolbox. In this work, we develop such a model to describe uptake of pesticide spray droplets across the leaf surface. We simplify the leaf structure by identifying the outer cuticle as the main barrier to uptake; the result is a novel, hybrid model in which two well-mixed compartments are separated by a membrane in which we describe the spatio-temporal distribution of the pesticide. This leads to a boundary value partial differential equation problem coupled to a pair of ordinary differential equation systems which we solve numerically. We also simplify the pesticide formulation into two key components: the Active Ingredient which produces the desired effect of the pesticide and an Adjuvant which is present in the formulation to facilitate effective absorption of the Active Ingredient into the leaf. This approach gives rise to concentration-dependent diffusion. We take an intuitive approach to parameter estimation using a small experimental data set and subsequently demonstrate the importance of the concentration-dependent diffusion in replicating the data. Finally, we demonstrate the need for further work to identify how the physicochemical properties of pesticides affect flow into and across the leaf surface