Endocrine and immune responses to resistance training in prostate cancer patients

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

Multifocal urothelial cancers with the mutator phenotype are of monoclonal origin and require panurothelial treatment for tumor clearance

Purpose: UC is a disease of the entire urothelium, characterized by multiplicity and multifocality. The clonal relationship among multiple UCs has implications regarding adjuvant chemotherapy. It has been investigated in studies of chromosomal alteration and single gene mutation. However, these genetic changes can occur in unrelated tumors under similar carcinogenic selection pressures. Tumors with high MSI have numerous DNA mutations, of which many provide no selection benefit. While these tumors represent an ideal model for studying UC clonality, their low frequency has prevented their previous investigation. Materials and Methods: We investigated 32 upper and lower urinary tract UCs with high MSI and 4 nonUC primary cancers in 9 patients. We used the high frequency and specificity of individual DNA mutations in these tumors (MSI at 17 loci) and the early timing of epigenetic events (methylation of 7 gene promoters) to investigate tumor clonality. Results: Molecular alterations varied among tumors from different primary organs but they appeared related in the UCs of all 9 patients. While 7 patients had a high degree of concordance among UCs, in 2 the UCs shared only a few similar alterations. Genetic and epigenetic abnormalities were frequently found in normal urothelial samples. Conclusions: Multiple UCs in each patient appeared to arise from a single clone. The molecular order of tumor development varied from the timing of clinical presentation and suggested that residual malignant cells persist in the urinary tract despite apparent curative surgery. These cells lead to subsequent tumor relapse and new methods are required to detect and eradicate them.

The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

Innate and adaptive immunity at mucosal surfaces of the female reproductive tract : stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

The Coorong and Lower Lakes : Talking fish - making connections with the rivers of the Murray-Darling Basin

After gathering water from 23 river valleys, the Murray empties into Lakes Alexandrina and Albert before making its way to the Coorong and out the Murray Mouth to Encounter Bay in South Australia. The entire Murray‐Darling Basin is upstream. Everything that happens there affects what goes on here...

Image-guided sampling reveals increased stroma and lower glandular complexity in mammographically dense breast tissue

Mammographic density (MD) adjusted for age and body mass index (BMI) is a strong heritable breast cancer risk factor; however, its biological basis remains elusive. Previous studies assessed MD-associated histology using random sampling approaches, despite evidence that high and low MD areas exist within a breast and are negatively correlated with respect to one another. We have used an image-guided approach to sample high and low MD tissues from within individual breasts to examine the relationship between histology and degree of MD. Image-guided sampling was performed using two different methodologies on mastectomy tissues (n = 12): (1) sampling of high and low MD regions within a slice guided by bright (high MD) and dark (low MD) areas in a slice X-ray film; (2) sampling of high and low MD regions within a whole breast using a stereotactically guided vacuum-assisted core biopsy technique. Pairwise analysis accounting for potential confounders (i.e. age, BMI, menopausal status, etc.) provides appropriate power for analysis despite the small sample size. High MD tissues had higher stromal (P = 0.002) and lower fat (P = 0.002) compositions, but no evidence of difference in glandular areas (P = 0.084) compared to low MD tissues from the same breast. High MD regions had higher relative gland counts (P = 0.023), and a preponderance of Type I lobules in high MD compared to low MD regions was observed in 58% of subjects (n = 7), but did not achieve significance. These findings clarify the histologic nature of high MD tissue and support hypotheses regarding the biophysical impact of dense connective tissue on mammary malignancy. They also provide important terms of reference for ongoing analyses of the underlying genetics of MD.

Advanced pubertal status at age 11 and lower physical activity in adolescent girls

Objective To examine the relationship between pubertal timing and physical activity. Study design A longitudinal sample of 143 adolescent girls was assessed at ages 11 and 13 years. Girls' pubertal development was assessed at age 11 with blood estradiol levels, Tanner breast staging criteria, and parental report of pubertal development. Girls were classified as early maturers (n = 41) or later maturers (n = 102) on the basis of their scores on the 3 pubertal development measures. Dependent variables measured at age 13 were average minutes/day of moderate to vigorous and vigorous physical activity as measured by the ActiGraph accelerometer. Results Early-maturing girls had significantly lower self-reported physical activity and accumulated fewer minutes of moderate to vigorous and vigorous physical activity and accelerometer counts per day at age 13 than later maturing girls. These effects v.-ere independent of differences in percentage body fat and self-reported physical activity at age 11. Conclusion Girls experiencing early pubertal maturation at age 11 reported lower subsequent physical activity at age 13 than their later maturing peers. Pubertal maturation, in particular early maturation relative to peers, may lead to declines in physical activity among adolescent girls.

Error and variance bounds on sigmoidal neurons with weight and input errors

Bounds on the expectation and variance of errors at the output of a multilayer feedforward neural network with perturbed weights and inputs are derived. It is assumed that errors in weights and inputs to the network are statistically independent and small. The bounds obtained are applicable to both digital and analogue network implementations and are shown to be of practical value.

Lower mantle diamonds from Rio Soriso (Juina area, Mato Grosso, Brazil)

The morphology, colour, fluorescence, cathodoluminescence, nitrogen content and aggregation state, internal structure and mineral inclusions have been studied for 69 alluvial diamonds from the Rio Soriso (Juina area, Mato Grosso State, Brazil). Nitrogen in most diamonds (53%) is fully aggregated as B centres, but there is also a large proportion of N-free stones (38%). A strong positive correlation between nitrogen and IR-active hydrogen concentrations is observed. The diamonds contain (in order of decreasing abundance) ferropericlase, CaSi-perovskite, magnetite, MgSi-perovskite, pyrrhotite, 'olivine', SiO2, perovskite, tetragonal almandine-pyrope phase and some other minerals represented by single grains. The Rio Soriso diamond suite is subdivided into several subpopulations that originated in upper and lower mantle of ultramafic and mafic compositions, with the largest subgroup forming in the ultramafic lower mantle. Analysed ferropericlase grains are enriched in Fe (Mg#=0.43-0.89), which is ascribed to their origin in the lowermost mantle. The Juina kimberlites may be unique in sampling the material from depths below 1,700 km that ascended in a plume formed at the core-mantle boundary.

Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Eyelid pressure on the cornea

The eyelids play an important role in lubricating and protecting the surface of the eye. Each blink serves to spread fresh tears, remove debris and replenish the smooth optical surface of the eye. Yet little is known about how the eyelids contact the ocular surface and what pressure distribution exists between the eyelids and cornea. As the principal refractive component of the eye, the cornea is a major element of the eye’s optics. The optical properties of the cornea are known to be susceptible to the pressure exerted by the eyelids. Abnormal eyelids, due to disease, have altered pressure on the ocular surface due to changes in the shape, thickness or position of the eyelids. Normal eyelids also cause corneal distortions that are most often noticed when they are resting closer to the corneal centre (for example during reading). There were many reports of monocular diplopia after reading due to corneal distortion, but prior to videokeratoscopes these localised changes could not be measured. This thesis has measured the influence of eyelid pressure on the cornea after short-term near tasks and techniques were developed to quantify eyelid pressure and its distribution. The profile of the wave-like eyelid-induced corneal changes and the refractive effects of these distortions were investigated. Corneal topography changes due to both the upper and lower eyelids were measured for four tasks involving two angles of vertical downward gaze (20° and 40°) and two near work tasks (reading and steady fixation). After examining the depth and shape of the corneal changes, conclusions were reached regarding the magnitude and distribution of upper and lower eyelid pressure for these task conditions. The degree of downward gaze appears to alter the upper eyelid pressure on the cornea, with deeper changes occurring after greater angles of downward gaze. Although the lower eyelid was further from the corneal centre in large angles of downward gaze, its effect on the cornea was greater than that of the upper eyelid. Eyelid tilt, curvature, and position were found to be influential in the magnitude of eyelid-induced corneal changes. Refractively these corneal changes are clinically and optically significant with mean spherical and astigmatic changes of about 0.25 D after only 15 minutes of downward gaze (40° reading and steady fixation conditions). Due to the magnitude of these changes, eyelid pressure in downward gaze offers a possible explanation for some of the day-to-day variation observed in refraction. Considering the magnitude of these changes and previous work on their regression, it is recommended that sustained tasks performed in downward gaze should be avoided for at least 30 minutes before corneal and refractive assessment requiring high accuracy. Novel procedures were developed to use a thin (0.17 mm) tactile piezoresistive pressure sensor mounted on a rigid contact lens to measure eyelid pressure. A hydrostatic calibration system was constructed to convert raw digital output of the sensors to actual pressure units. Conditioning the sensor prior to use regulated the measurement response and sensor output was found to stabilise about 10 seconds after loading. The influences of various external factors on sensor output were studied. While the sensor output drifted slightly over several hours, it was not significant over the measurement time of 30 seconds used for eyelid pressure, as long as the length of the calibration and measurement recordings were matched. The error associated with calibrating at room temperature but measuring at ocular surface temperature led to a very small overestimation of pressure. To optimally position the sensor-contact lens combination under the eyelid margin, an in vivo measurement apparatus was constructed. Using this system, eyelid pressure increases were observed when the upper eyelid was placed on the sensor and a significant increase was apparent when the eyelid pressure was increased by pulling the upper eyelid tighter against the eye. For a group of young adult subjects, upper eyelid pressure was measured using this piezoresistive sensor system. Three models of contact between the eyelid and ocular surface were used to calibrate the pressure readings. The first model assumed contact between the eyelid and pressure sensor over more than the pressure cell width of 1.14 mm. Using thin pressure sensitive carbon paper placed under the eyelid, a contact imprint was measured and this width used for the second model of contact. Lastly as Marx’s line has been implicated as the region of contact with the ocular surface, its width was measured and used as the region of contact for the third model. The mean eyelid pressures calculated using these three models for the group of young subjects were 3.8 ± 0.7 mmHg (whole cell), 8.0 ± 3.4 mmHg (imprint width) and 55 ± 26 mmHg (Marx’s line). The carbon imprints using Pressurex-micro confirmed previous suggestions that a band of the eyelid margin has primary contact with the ocular surface and provided the best estimate of the contact region and hence eyelid pressure. Although it is difficult to directly compare the results with previous eyelid pressure measurement attempts, the eyelid pressure calculated using this model was slightly higher than previous manometer measurements but showed good agreement with the eyelid force estimated using an eyelid tensiometer. The work described in this thesis has shown that the eyelids have a significant influence on corneal shape, even after short-term tasks (15 minutes). Instrumentation was developed using piezoresistive sensors to measure eyelid pressure. Measurements for the upper eyelid combined with estimates of the contact region between the cornea and the eyelid enabled quantification of the upper eyelid pressure for a group of young adult subjects. These techniques will allow further investigation of the interaction between the eyelids and the surface of the eye.

Use of Bayesian MUNE to show differing rate of loss of motor units in subgroups of ALS

Objectives To evaluate differences among patients with different clinical features of ALS, we used our Bayesian method of motor unit number estimation (MUNE). Methods We performed serial MUNE studies on 42 subjects who fulfilled the diagnostic criteria for ALS during the course of their illness. Subjects were classified into three subgroups according to whether they had typical ALS (with upper and lower motor neurone signs) or had predominantly upper motor neurone weakness with only minor LMN signs, or predominantly lower motor neurone weakness with only minor UMN signs. In all subjects we calculated the half life of MUs, defined as the expected time for the number of MUs to halve, in one or more of the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles. Results The mean half life of MUs was less in subjects who had typical ALS with both upper and lower motor neurone signs than in those with predominantly upper motor neurone weakness or predominantly lower motor neurone weakness. In 18 subjects we analysed the estimated size of the MUs and demonstrated the appearance of large MUs in subjects with upper or lower motor neurone predominant weakness. We found that the appearance of large MUs was correlated with the half life of MUs. Conclusions Patients with different clinical features of ALS have different rates of loss and different sizes of MUs. Significance: These findings could indicate differences in disease pathogenesis.

Application of an appearance-based intervention to improve sun protection outcomes of outdoor workers in Queensland, Australia

Outdoor workers are exposed to high levels of ultraviolet radiation (UVR) and may thus be at greater risk to experience UVR-related health effects such as skin cancer, sun burn, and cataracts. A number of intervention trials (n=14) have aimed to improve outdoor workers’ work-related sun protection cognitions and behaviours. Only one study however has reported the use of UV-photography as part of a multi-component intervention. This study was performed in the USA and showed long-term (12 months) improvements in work-related sun protection behaviours. Intervention effects of the other studies have varied greatly, depending on the population studied, intervention applied, and measurement of effect. Previous studies have not assessed whether: - Interventions are similarly effective for workers in stringent and less stringent policy organisations; - Policy effect is translated into workers’ leisure time protection; - Implemented interventions are effective in the long-term; - The facial UV-photograph technique is effective in Australian male outdoor workers without a large additional intervention package, and; - Such interventions will also affect workers’ leisure time sun-related cognitions and behaviours. Therefore, the present Protection of Outdoor Workers from Environmental Radiation [POWER]-study aimed to fill these gaps and had the objectives of: a) assessing outdoor workers’ sun-related cognitions and behaviours at work and during leisure time in stringent and less stringent sun protection policy environments; b) assessing the effect of an appearance-based intervention on workers’ risk perceptions, intentions and behaviours over time; c) assessing whether the intervention was equally effective within the two policy settings; and d) assessing the immediate post-intervention effect. Effectiveness was described in terms of changes in sun-related risk perceptions and intentions (as these factors were shown to be main precursors of behaviour change in many health promotion theories) and behaviour. The study purposefully selected and recruited two organisations with a large outdoor worker contingent in Queensland, Australia within a 40 kilometre radius of Brisbane. The two organisations differed in the stringency of implementation and reinforcement of their organisational sun protection policy. Data were collected from 154 male predominantly Australian born outdoor workers with an average age of 37 years and predominantly medium to fair skin (83%). Sun-related cognitions and behaviours of workers were assessed using self-report questionnaires at baseline and six to twelve months later. Variation in follow-up time was due to a time difference in the recruitment of the two organisations. Participants within each organisation were assigned to an intervention or control group. The intervention group participants received a one-off personalised Skin Cancer Risk Assessment Tool [SCRAT]-letter and a facial UV-photograph with detailed verbal information. This was followed by an immediate post-intervention questionnaire within three months of the start of the study. The control group only received the baseline and follow-up questionnaire. Data were analysed using a variety of techniques including: descriptive analyses, parametric and non-parametric tests, and generalised estimating equations. A 15% proportional difference observed was deemed of clinical significance, with the addition of reported statistical significance (p<0.05) where applicable. Objective 1: Assess and compare the current sun-related risk perceptions, intentions, behaviours, and policy awareness of outdoor workers in stringent and less stringent sun protection policy settings. Workers within the two organisations (stringent n=89 and less stringent n=65) were similar in their knowledge about skin cancer, self efficacy, attitudes, and social norms regarding sun protection at work and during leisure time. Participants were predominantly in favour of sun protection. Results highlighted that compared to workers in a less stringent policy organisation working for an organisation with stringent sun protection policies and practices resulted in more desirable sun protection intentions (less willing to tan p=0.03) ; actual behaviours at work (sufficient use of upper and lower body protection, headgear, and sunglasses (p<0.001 for all comparisons), and greater policy awareness (awareness of repercussions if Personal Protective Equipment (PPE) was not used, p<0.001)). However the effect of the work-related sun protection policy was found not to extend to leisure time sun protection. Objective 2: Compare changes in sun-related risk perceptions, intentions, and behaviours between the intervention and control group. The effect of the intervention was minimal and mainly resulted in a clinically significant reduction in work-related self-perceived risk of developing skin cancer in the intervention compared to the control group (16% and 32% for intervention and control group, respectively estimated their risk higher compared to other outdoor workers: , p=0.11). No other clinical significant effects were observed at 12 months follow-up. Objective 3: Assess whether the intervention was equally effective in the stringent sun protection policy organisation and the less stringent sun protection policy organisation. The appearance-based intervention resulted in a clinically significant improvement in the stringent policy intervention group participants’ intention to protect from the sun at work (workplace*time interaction, p=0.01). In addition to a reduction in their willingness to tan both at work (will tan at baseline: 17% and 61%, p=0.06, at follow-up: 54% and 33%, p=0.07, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p<0.001) and during leisure time (will tan at baseline: 42% and 78%, p=0.01, at follow-up: 50% and 63%, p=0.43, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p=0.01) over the course of the study compared to the less stringent policy intervention group. However, no changes in actual sun protection behaviours were found. Objective 4: Examine the effect of the intervention on level of alarm and concern regarding the health of the skin as well as sun protection behaviours in both organisations. The immediate post-intervention results showed that the stringent policy organisation participants indicated to be less alarmed (p=0.04) and concerned (p<0.01) about the health of their skin and less likely to show the facial UV-photograph to others (family p=0.03) compared to the less stringent policy participants. A clinically significantly larger proportion of participants from the stringent policy organisation reported they worried more about skin cancer (65%) and skin freckling (43%) compared to those in the less stringent policy organisation (46%,and 23% respectively , after seeing the UV-photograph). In summary the results of this study suggest that the having a stringent work-related sun protection policy was significantly related to for work-time sun protection practices, but did not extend to leisure time sun protection. This could reflect the insufficient level of sun protection found in the general Australian population during leisure time. Alternatively, reactance caused by being restricted in personal decisions through work-time policy could have contributed to lower leisure time sun protection. Finally, other factors could have also contributed to the less than optimal leisure time sun protection behaviours reported, such as unmeasured personal or cultural barriers. All these factors combined may have lead to reduced willingness to take proper preventive action during leisure time exposure. The intervention did not result in any measurable difference between the intervention and control groups in sun protection behaviours in this population, potentially due to the long lag time between the implementation of the intervention and assessment at 12-months follow-up. In addition, high levels of sun protection behaviours were found at baseline (ceiling effect) which left little room for improvement. Further, this study did not assess sunscreen use, which was the predominant behaviour assessed in previous effective appearance-based interventions trials. Additionally, previous trials were mainly conducted in female populations, whilst the POWER-study’s population was all male. The observed immediate post-intervention result could be due to more emphasis being placed on sun protection and risks related to sun exposure in the stringent policy organisation. Therefore participants from the stringent policy organisation could have been more aware of harmful effects of UVR and hence, by knowing that they usually protect adequately, not be as alarmed or concerned as the participants from the less stringent policy organisation. In conclusion, a facial UV-photograph and SCRAT-letter information alone may not achieve large changes in sun-related cognitions and behaviour, especially of assessed 6-12 months after the intervention was implemented and in workers who are already quite well protected. Differences found between workers in the present study appear to be more attributable to organisational policy. However, against a background of organisational policy, this intervention may be a useful addition to sun-related workplace health and safety programs. The study findings have been interpreted while respecting a number of limitations. These have included non-random allocation of participants due to pre-organised allocation of participants to study group in one organisation and difficulty in separating participants from either study group. Due to the transient nature of the outdoor worker population, only 105 of 154 workers available at baseline could be reached for follow-up. (attrition rate=32%). In addition the discrepancy in the time to follow-up assessment between the two organisations was a limitation of the current study. Given the caveats of this research, the following recommendations were made for future research: - Consensus should be reached to define "outdoor worker" in terms of time spent outside at work as well as in the way sun protection behaviours are measured and reported. - Future studies should implement and assess the value of the facial UV-photographs in a wide range of outdoor worker organisations and countries. - More timely and frequent follow-up assessments should be implemented in intervention studies to determine the intervention effect and to identify the best timing of booster sessions to optimise results. - Future research should continue to aim to target outdoor workers’ leisure time cognitions and behaviours and improve these if possible. Overall, policy appears to be an important factor in workers’ compliance with work-time use of sun protection. Given the evidence generated by this research, organisations employing outdoor workers should consider stringent implementation and reinforcement of a sun protection policy. Finally, more research is needed to improve ways to generate desirable behaviour in this population during leisure time.