Trauma and Family Therapy: Reflections on September 11 from Northern Ireland

This article draws on the author's experience of living and working in Belfast, Northern Ireland. Connections between the traumatic events of September 11 and the situation in the north of Ireland of ongoing civil conflict and violence are developed and aspects of therapeutic practice are described. Coping with the effects of trauma presents systemic therapists with multiple and complex challenges in whatever sociopolitical context they practice. A therapist stance that combines flexibility and openness of attitude with the creative use of therapeutic practices, including those from other modalities, will assist systemic therapists in rising to these challenges.

Drug Delivery of Aminolevulinic Acid from Topical Formulations Intended for Photodynamic Therapy

Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing
cells. Cell destruction occurs when PpIx is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in
relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations.

The intraocular lens: challenges in the prevention and therapy of infectious endophthalmitis and posterior capsular opacification

Cataract is the leading cause of visual impairment worldwide. In the UK, some 30% of the population over 65 years of age have visually impairing cataract. Importantly, 88% of those with treatable visual impairment from cataract are not in contact with any ocular healthcare service, representing a major potential healthcare need [1]. In the USA, it has been estimated that 17.2% of the population (approximately 20.5 million) over 40 years of age have cataract in either eye and by 2020, this number is expected to rise to 30.1 million. Currently, cataract is responsible for 60% of Medicare costs associated with vision [2]. Furthermore, as the populations of industrialized countries such as the UK and the USA continue to age, the costs associated with treatment of cataract can only be expected to increase. Consequently, the development of the intraocular lens to replace the cataractous lens and the advances in intraocular lens design and implantation represent a major development in cataract treatment. However, despite such advances, cataract surgery is not without complications, such as postoperative infectious endophthalmitis, a rare but potentially devastating condition, and posterior capsular opacification, a less serious but much more common problem. This review will examine the epidemiology of cataracts, the polymeric construction of intraocular lenses implanted during cataract surgery and the complications of postoperative infectious endophthalmitis and posterior capsular opacification with regard to therapeutic interventions and prophylactic strategies. Advances in biomaterial design and function will be discussed as novel approaches to prevent such postoperative complications.

Monocyte-derived dendritic cells: a potential target for therapy in multiple sclerosis (MS)

Monocytes can differentiate into dendritic cells (DC), cells with a pivotal role in both protective immunity and tolerance. Defects in the maturation or function of DC may be important in the development of autoimmune disease. We sought to establish if there were differences in the cytokine (granulocyte-macrophage colony-stimulating factor and IL-4)-driven maturation of monocytes to DC in patients with MS and whether drugs used to treat MS affected this process in vitro. We have demonstrated that there is no defect in the ability of magnetic activated cell sorting (MACS)-purified monocytes from patients with MS to differentiate to DC, but equally they show no tendency to acquire a DC phenotype without exogenous cytokines. Interferon-beta1a prevents the acquisition of a full DC phenotype as determined by light and electron microscopy and by flow cytometry. Methylprednisolone not only prevents the development of monocyte-derived DC but totally redirects monocyte differentiation towards a macrophage phenotype. Evidence is evolving for a role for DC in central nervous system immunity, either within the brain or in cervical lymph nodes. The demonstrated effect of both drugs on monocyte differentiation may represent an important site for immune therapy in MS.

Reconstructing the dynamics of a movable mirror in a detuned optical cavity

We consider the dynamics of a movable mirror in a Fabry-Perot cavity coupled through radiation pressure to the cavity field and in contact with a thermal bath at finite temperature. In contrast to previous approaches, we consider arbitrary values of the effective detuning between the cavity and an external input field. We analyse the radiation-pressure effect on the Brownian motion of the mirror and its significance in the density noise spectrum of the output cavity field. Important properties of the mirror dynamics can be gathered directly from this noise spectrum. The presented reconstruction provides an experimentally useful tool in the characterization of the energy and rigidity of the mirror as modified by the coupling with light. We also give a quantitative analysis of the recent experimental observation of self-cooling of a micromechanical oscillator.

Self-cooling of a micro-mirror by radiation pressure

Cooling of mechanical resonators is currently a popular topic in many fields of physics including ultra-high precision measurements, detection of gravitational waves and the study of the transition between classical and quantum behaviour of a mechanical system. Here we report the observation of self-cooling of a micromirror by radiation pressure inside a high-finesse optical cavity. In essence, changes in intensity in a detuned cavity, as caused by the thermal vibration of the mirror, provide the mechanism for entropy flow from the mirror's oscillatory motion to the low-entropy cavity field. The crucial coupling between radiation and mechanical motion was made possible by producing free-standing micromirrors of low mass (m approximately 400 ng), high reflectance (more than 99.6%) and high mechanical quality (Q approximately 10,000). We observe cooling of the mechanical oscillator by a factor of more than 30; that is, from room temperature to below 10 K. In addition to purely photothermal effects we identify radiation pressure as a relevant mechanism responsible for the cooling. In contrast with earlier experiments, our technique does not need any active feedback. We expect that improvements of our method will permit cooling ratios beyond 1,000 and will thus possibly enable cooling all the way down to the quantum mechanical ground state of the micromirror.