Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime.

The low-latitude boundary layer: Application of ISTP advances to past data

The destruction of the four Cluster craft was a major loss to the planned ISTP effort, of which studies of the magnetopause and low-latitude boundary layer (LLBL) were an important part. While awaiting the re-flight mission, Cluster-II, we have been applying advances in our understanding made using other ISTP craft (like Polar and Wind) and using ground-based facilities (in particular the EISCAT incoherent scatter radars and the SuperDARN HF coherent radars) to measurements of the LLBL made in 1984 and 1985 by the AMPTE-UKS and -IRM spacecraft pair. In particular, one unexplained result of the AMPTE mission was that the electron characteristics could, in nearly all cases, order independent measurements near the magnetopause, such as the magnetic field, ion temperatures and the plasma flow. Studies of the cusp have shown that the precipitation is ordered by the time-elapsed since the field line was opened by reconnection. This insight has allowed us to reanalyse the AMPTE data and show that the ordering by the transition parameter is also due to the variation of time elapsed since reconnection, with the important implication that reconnection usually coats most of the dayside magnetopause with at least some newly-opened field lines. In addition, we can use the electron characteristics to isolate features like RDs, slow-mode shocks and slow-mode expansion fans. The ion characteristics can be used to compute the reconnection rate. We here retrospectively apply these new techniques, developed in the ISTP era, to a much-studied flux transfer event observed by the AMPTE satellites. As a result, we gain new understanding of its cause and structure.

Advances in the study of boundary value problems for nonlinear integrable PDEs

In this review I summarise some of the most significant advances of the last decade in the analysis and solution of boundary value problems for integrable partial differential equations in two independent variables. These equations arise widely in mathematical physics, and in order to model realistic applications, it is essential to consider bounded domain and inhomogeneous boundary conditions. I focus specifically on a general and widely applicable approach, usually referred to as the Unified Transform or Fokas Transform, that provides a substantial generalisation of the classical Inverse Scattering Transform. This approach preserves the conceptual efficiency and aesthetic appeal of the more classical transform approaches, but presents a distinctive and important difference. While the Inverse Scattering Transform follows the "separation of variables" philosophy, albeit in a nonlinear setting, the Unified Transform is a based on the idea of synthesis, rather than separation, of variables. I will outline the main ideas in the case of linear evolution equations, and then illustrate their generalisation to certain nonlinear cases of particular significance.

Advances in the stochastic modelling of satellite-derived rainfall estimates using a sparse calibration dataset

As satellite technology develops, satellite rainfall estimates are likely to become ever more important in the world of food security. It is therefore vital to be able to identify the uncertainty of such estimates and for end users to be able to use this information in a meaningful way. This paper presents new developments in the methodology of simulating satellite rainfall ensembles from thermal infrared satellite data. Although the basic sequential simulation methodology has been developed in previous studies, it was not suitable for use in regions with more complex terrain and limited calibration data. Developments in this work include the creation of a multithreshold, multizone calibration procedure, plus investigations into the causes of an overestimation of low rainfall amounts and the best way to take into account clustered calibration data. A case study of the Ethiopian highlands has been used as an illustration.

Technical note: how accurate can stalagmite formation temperatures be determined using vapour bubble radius measurements in fluid inclusions?

Stalagmites are natural archives containing detailed information on continental climate variability of the past. Microthermometric measurements of fluid inclusion homogenisation temperatures allow determination of stalagmite formation temperatures by measuring the radius of stable laser-induced vapour bubbles inside the inclusions. A reliable method for precisely measuring the radius of vapour bubbles is presented. The method is applied to stalagmite samples for which the formation temperature is known. An assessment of the bubble radius measurement accuracy and how this error influences the uncertainty in determining the formation temperature is provided. We demonstrate that the nominal homogenisation temperature of a single inclusion can be determined with an accuracy of ±0.25 °C, if the volume of the inclusion is larger than 105 μm3. With this method, we could measure in a proof-of-principle investigation that the formation temperature of 10–20 yr old inclusions in a stalagmite taken from the Milandre cave is 9.87 ± 0.80 °C, while the mean annual surface temperature, that in the case of the Milandre cave correlates well with the cave temperature, was 9.6 ± 0.15 °C, calculated from actual measurements at that time, showing a very good agreement. Formation temperatures of inclusions formed during the last 450 yr are found in a temperature range between 8.4 and 9.6 °C, which corresponds to the calculated average surface temperature. Paleotemperatures can thus be determined within ±1.0 °C.

Advances in understanding mineral dust and boundary layer processes over the Sahara from Fennec aircraft observations

The Fennec climate program aims to improve understanding of the Saharan climate system through a synergy of observations and modelling. We present a description of the Fennec airborne observations during 2011 and 2012 over the remote Sahara (Mauritania and Mali) and the advances in the understanding of mineral dust and boundary layer processes they have provided. Aircraft instrumentation aboard the UK FAAM BAe146 and French SAFIRE Falcon 20 is described, with specific focus on instrumentation specially developed and relevant to Saharan meteorology and dust. Flight locations, aims and associated meteorology are described. Examples and applications of aircraft measurements from the Fennec flights are presented, highlighting new scientific results delivered using a synergy of different instruments and aircraft. These include: (1) the first airborne measurement of dust particles sized up to 300 microns and associated dust fluxes in the Saharan atmospheric boundary layer (SABL), (2) dust uplift from the breakdown of the nocturnal low-level jet before becoming visible in SEVIRI satellite imagery, (3) vertical profiles of the unique vertical structure of turbulent fluxes in the SABL, (4) in-situ observations of processes in SABL clouds showing dust acting as CCN and IN at −15 °C, (5) dual-aircraft observations of the SABL dynamics, thermodynamics and composition in the Saharan heat low region (SHL), (6) airborne observations of a dust storm associated with a cold-pool (haboob) issued from deep convection over the Atlas, (7) the first airborne chemical composition measurements of dust in the SHL region with differing composition, sources (determined using Lagrangian backward trajectory calculations) and absorption properties between 2011 and 2012, (8) coincident ozone and dust surface area measurements suggest coarser particles provide a route for ozone depletion, (9) discrepancies between airborne coarse mode size distributions and AERONET sunphotometer retrievals under light dust loadings. These results provide insights into boundary layer and dust processes in the SHL region – a region of substantial global climatic importance.

Understanding advances in the simulation of the Madden-Julian Oscillation in a numerical weather prediction model.

The Madden-Julian Oscillation (MJO) is the dominant mode of intraseasonal variability in the Trop- ics. It can be characterised as a planetary-scale coupling between the atmospheric circulation and organised deep convection that propagates east through the equatorial Indo-Pacific region. The MJO interacts with weather and climate systems on a near-global scale and is a crucial source of predictability for weather forecasts on medium to seasonal timescales. Despite its global signifi- cance, accurately representing the MJO in numerical weather prediction (NWP) and climate models remains a challenge. This thesis focuses on the representation of the MJO in the Integrated Forecasting System (IFS) at the European Centre for Medium-Range Weather Forecasting (ECMWF), a state-of-the-art NWP model. Recent modifications to the model physics in Cycle 32r3 (Cy32r3) of the IFS led to ad- vances in the simulation of the MJO; for the first time the observed amplitude of the MJO was maintained throughout the integration period. A set of hindcast experiments, which differ only in their formulation of convection, have been performed between May 2008 and April 2009 to asses the sensitivity of MJO simulation in the IFS to the Cy32r3 convective parameterization. Unique to this thesis is the attribution of the advances in MJO simulation in Cy32r3 to the mod- ified convective parameterization, specifically, the relative-humidity-dependent formulation for or- ganised deep entrainment. Increasing the sensitivity of the deep convection scheme to environmen- tal moisture is shown to modify the relationship between precipitation and moisture in the model. Through dry-air entrainment, convective plumes ascending in low-humidity environments terminate lower in the atmosphere. As a result, there is an increase in the occurrence of cumulus congestus, which acts to moisten the mid-troposphere. Due to the modified precipitation-moisture relationship more moisture is able to build up which effectively preconditions the tropical atmosphere for the transition to deep convection. Results from this thesis suggest that a tropospheric moisture control on convection is key to simulating the interaction between the physics and large-scale circulation associated with the MJO.

Advances in Discourse Studies

Methods of approaching the study of discourse have developed rapidly in the last ten years, influenced by a growing interdisciplinary spirit among linguistics and anthropology, sociology, cognitive and cultural psychology and cultural studies, as well as among established sub-fields within linguistics itself. Among the more recent developments are an increasing ‘critical’ turn in discourse analysis, a growing interest in historical, ethnographic and corpus-based approaches to discourse, more concern with the social contexts in which discourse occurs, the social actions that it is used to take and the identities that are constructed through it, as well as a revaluation of what counts as ‘discourse’ to include multi-modal texts and interaction. Advances in Discourse Studies brings together contributions from leading scholars in the field, investigating the historical and theoretical relationships between new advances in discourse studies and pointing towards new directions for the future of the discipline. Featuring discussion questions, classroom projects and recommended readings at the end of each section, as well as case studies illustrating each approach discussed, this is an invaluable resource for students of interdisciplinary discourse analysis.

Optimizing the nipple-areola sparing mastectomy with double concentric periareolar incision and biodimensional expander-implant reconstruction: Aesthetic and technical refinements

Although the biodimensional anatomical expander-implant system (BEIS) is a reliable technique, little information has been available regarding outcome following nipple-areola sparing mastectomy (NSM). To perform the resection of glandular tissue, while improving the surgical access and maintaining the nipple-areola vascularization we have developed a new approach for NSM based on the double concentric periareolar incision (DCPI). The purpose of this study is to analyze the feasibility, surgical planning and its outcome following NSM. 18 patients underwent NSM reconstructions. Mean time of follow-up was 29 months. The technique was indicated in patients with small/moderate volume breasts. Flap complications were evaluated and information on aesthetic results and patient satisfaction were collected. 83.3% had tumors measuring 2 cm or less (T1) and 72.1% were stage 0 and 1. All patients presented peripherally tumors located (at least 5 cm from the nipple). Skin complications occurred in 11.1%. One patient (5.5%) presented small skin necrosis and a wound dehiscence was observed in one patient (5.5%). The aesthetic result was good/very good in 94.4 percent and the majority of patients were very satisfied/satisfied. No local recurrences were observed. All complications except one were treated by a conservative approach. DCPI-BEIS is a simple and reliable technique for NSM reconstruction. The success depends on patient selection, coordinated planning with the oncologic surgeon and careful intra-operative and post-operative management. (C) 2009 Elsevier Ltd. All rights reserved.