Assessing inter and intrafraction uncertainties in adult brain cancer patients using 2D/3D kV and CBCT imaging.

METHOD: 2D/3D kV imaging and CBCT data using 6 degrees of freedom (6DoF) were compared to evaluate inter and intrafraction motion. RESULTS: Results showed that intrafraction errors were low and interfraction levels were within institutional protocols. CONCLUSION: Confidence was given to use low dose 2D/3D kV imaging to confirm daily patient set up errors, and to use pre-treatment CBCT only once weekly for additional imaging information. IMPLICATIONS FOR PRACTICE: Further research is necessary to assess other uncertainties, to enable the calculation of a margin and determining the feasibility of further reduction of this.

How much disease risk is due to old age and established risk factors?

Improved healthcare is leading to older populations and increasing numbers of individuals experiencing multiple diseases, possibly concurrently (multimorbidity). This article asks whether the observed number of new diseases is more than expected based on age and established risk factors alone, assuming that disease risk is unchanged by prior or pre-existing disease. This is accomplished by designing a new epidemiological approach, where the expected number of disease types are estimated for individuals without prior disease, by combining individual risk predictions with a "Poisson-Binomial" model to estimate the expected number of new diseases and its confidence interval. For 123 diseases in men and 99 diseases in women, the expected number of new diseases based on age and established risk factors was approximately 2/3 of that observed, with the observed number of new diseases approximately 1.5 times that predicted. The differences could not be explained by natural statistical variation, and provide a rigorous statistical demonstration of lower disease risk for individuals without any previous disease. The multiple of 1.5 was sufficiently consistent across different diseases to prevent its use for classification of disease types, but there were differences for subgroups such as smokers with high body mass index, and for some classes of disease (as defined by the International Classification of Diseases, version 10). The results suggest that empirical modeling might allow reliable predictions of future hospital admissions, and confirm the value of conventional epidemiological approaches that study disease risk in healthy individuals. The implications and future possibilities of this new approach are discussed.

Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Surface guided radiation therapy: An international survey on current clinical practice.

Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods: A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results: Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors' recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions: This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines.

Active learning in head and neck trauma: outcomes after an innovative educational course.

Excellence in teaching and learning is fundamental to the provision of quality training for doctors and for this a sound knowledge of the principles of adult learning theory is important. We present an educational course in head and neck trauma skills for emergency medicine (EM) registrars, using the pedagogical principle of active learning. Our aim was to provide trainees with skills in the evaluation and management of hard and soft tissue injuries to the head, neck, and mouth. Active learning has been shown to provide a superior experience in classrooms, creating a 'deep' understanding of the material. To maximise learning, we used these principles to develop small group seminars led by a diverse range of teachers that allowed trainees to acquire hands-on skills. Questionnaires that were completed before and after the course showed an appreciable educational impact. We conclude that innovative teaching methods facilitate the sharing of knowledge that will benefit patient care.

A non-invasive assessment of essential trace element utilization at different trophic levels in African wildlife.

The complex relationships that exist between terrestrial mammals and their habitats make African ecosystems highly interactive environments. Anthropogenic activities including climate change have altered geochemical cycles, which influence nutrient availability and deficiency at local, regional and global scales. As synergistic and antagonistic interactions occur between essential elements at both deficiency and excess concentrations, the differences in feeding strategy between trophically distinct groups of terrestrial vertebrates are likely to influence the degree to which overall nutrient needs are met or may be deficient. The overall aim of this study was to investigate and compare quantitative differences of nine essential elements in terrestrial vertebrates occupying different trophic levels within two protected areas; Tswalu Kalahari Reserve (TKR) and Manyeleti Nature Reserve (MNR) South Africa, using faeces as an analytical matrix. Results from linear mixed effects models highlight that concentrations varied widely between individuals. Overall, measured concentrations above their respective means were evident for B and Mn in herbivores, Fe in omnivores and Cu, Co, Fe, Se and Zn in carnivores. Measured concentrations of Mo and Ni did not differ significantly between trophic groups. Although site-specific differences were evident for specific elements, measured mean concentrations of B, Co, Cu, Fe, Mo, Ni, Se and Zn were significantly higher overall at the MNR study site compared to the TKR site. This is the first study to non-invasively assess essential element concentrations across trophic levels in free ranging African wildlife species within protected areas of the savannah biome. Combined with the assessment of environmental matrices, this approach can be used as an effective diagnostic tool for the assessment of animal welfare and the management of protected areas globally.

Serological investigation of protozoan pathogens (Trypanosoma cruzi, Toxoplasma gondii and Neospora caninum) in opossums from southern Brazil.

South American opossums of the order Didelphimorphia are considered sentinels for zoonotic infections and environmental diseases, such as for Chagas disease caused by Trypanosoma cruzi. Nevertheless, there is a paucity of data regarding protozoan diseases such Toxoplasma gondii and Neospora caninum in Neotropical marsupials; despite these pathogens have been considered threats to some marsupial species. The aim of this study was to determine whether Didelphis albiventris and Philander frenatus opossums from southern Brazil had been previously exposed to T. cruzi, T. gondii or N. caninum. Opossum samples were obtained by live-trapping of free-ranging animals and collection at wildlife rehabilitation centers in Rio Grande do Sul (RS) state, Brazil. The detection of anti-T. cruzi and anti-T. gondii antibodies was performed by indirect hemagglutination and anti-N. caninum antibodies by competitive enzyme-linked immunosorbent assay. In total, samples were collected from 76 marsupials from nine municipalities in RS state, including 69 D. albiventris (white-eared opossum), and seven were P. frenatus (southern four-eyed opossum). For T. cruzi, 11% were seropositive, and for T. gondii 26% were seropositive. None of the marsupials sampled here were seropositive for N. caninum. Risk factor analysis showed that free-living animals were about five-fold more likely to be infected by T. gondii than were rescued animals. Our study showed the exposure of Neotropical marsupials (D. albiventris and P. frenatus) to protozoan pathogens T. cruzi and T. gondii, while no evidence of N. caninum exposure was found. The set of results presented here may have an effect on ecology and conservation of the studied species and may also indicate possible sentinels of these pathogen circulation.

Characterisation, identification, clustering, and classification of disease.

The importance of quantifying the distribution and determinants of multimorbidity has prompted novel data-driven classifications of disease. Applications have included improved statistical power and refined prognoses for a range of respiratory, infectious, autoimmune, and neurological diseases, with studies using molecular information, age of disease incidence, and sequences of disease onset ("disease trajectories") to classify disease clusters. Here we consider whether easily measured risk factors such as height and BMI can effectively characterise diseases in UK Biobank data, combining established statistical methods in new but rigorous ways to provide clinically relevant comparisons and clusters of disease. Over 400 common diseases were selected for analysis using clinical and epidemiological criteria, and conventional proportional hazards models were used to estimate associations with 12 established risk factors. Several diseases had strongly sex-dependent associations of disease risk with BMI. Importantly, a large proportion of diseases affecting both sexes could be identified by their risk factors, and equivalent diseases tended to cluster adjacently. These included 10 diseases presently classified as "Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified". Many clusters are associated with a shared, known pathogenesis, others suggest likely but presently unconfirmed causes. The specificity of associations and shared pathogenesis of many clustered diseases provide a new perspective on the interactions between biological pathways, risk factors, and patterns of disease such as multimorbidity.

The Development of Therapeutic Radiographers in Imaging and Adaptive Radiotherapy Through Clinical Trial Quality Assurance.

AIMS: Adaptive radiotherapy (ART) is an emerging advanced treatment option for bladder cancer patients. Therapeutic radiographers (RTTs) are central to the successful delivery of this treatment. The purpose of this work was to evaluate the image-guided radiotherapy (IGRT) and ART experience of RTTs before participating in the RAIDER trial. A plan of the day (PoD) quality assurance programme was then implemented. Finally, the post-trial experience of RTTs was evaluated, together with the impact of trial quality assurance participation on their routine practice. MATERIALS AND METHODS: A pre-trial questionnaire to assess the experience of the RTT staff group in IGRT and ART in bladder cancer was sent to each centre. Responses were grouped according to experience. The PoD quality assurance programme was implemented, and the RAIDER trial commenced. During stage 1 of the trial, RTTs reported difficulties in delivering PoD and the quality assurance programme was updated accordingly. A follow-up questionnaire was sent assessing experience in IGRT and ART post-trial. Any changes in routine practice were also recorded. RESULTS: The experience of RTTs in IGRT and ART pre-trial varied. For centres deemed to have RTTs with more experience, the initial PoD quality assurance programme was streamlined. For RTTs without ART experience, the full quality assurance programme was implemented, of which 508 RTTs completed. The quality assurance programme was updated (as the trial recruited) and it was mandated that at least one representative RTT (regardless of pre-trial experience) participated in the update in real-time. The purpose of the updated quality assurance programme was to provide further support to RTTs in delivering a complex treatment. Engagement with the updated quality assurance programme was high, with RTTs in 24/33 centres participating in the real-time online workshop. All 33 UK centres reported all RTTs reviewed the updated training offline. Post-trial, the RTTs' experience in IGRT and ART was increased. CONCLUSION: Overall, 508 RTTs undertook the PoD quality assurance programme. There was a high engagement of RTTs in the PoD quality assurance programme and trial. RTTs increased their experience in IGRT and ART and subsequently updated their practice for bladder cancer and other treatment sites.

The anorexigenic effect of adrenomedullin in Japanese quail (Coturnix japonica) involves increased proopiomelanocortin and cocaine- and amphetamine-regulated transcript mRNAs in the arcuate nucleus of the hypothalamus.

Central administration of adrenomedullin (AM), a 52-amino acid peptide, is associated with anorexigenic effects in some species, including rodents and chickens. However, the associated hypothalamic mechanisms remain unclear and it is unknown if this peptide exerts satiety-inducing effects in other avian species. The objective of this study was thus to investigate AM-induced anorexigenic effects in 7-day-old Japanese quail (Coturnix japonica). After intracerebroventricular injection of 0.3, 1.0, or 3.0 nmol of AM, quail injected with 3.0 nmol of AM ate and drank less than vehicle-injected quail at 180 min after injection. Except for the 1.0 nmol dose of AM exerting an anorexigenic effect at 90 min after injection, no other inhibitory effects on food or water intake were observed. At 60 min after injection, the AM-injected quail had more c-Fos immunoreactive cells in the arcuate nucleus (ARC) than vehicle-injected birds. In the ARC, AM injection was associated with increased proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNAs. In conclusion, the results suggest that the anorexigenic effect of AM is possibly influenced by the synergistic effect of POMC and CART in the ARC.

Image-Guided Radiotherapy for Pelvic Cancers: A Review of Current Evidence and Clinical Utilisation.

The meticulous selection and utilisation of image-guided radiotherapy (IGRT) are essential for optimal radiotherapy treatment delivery when using highly conformal treatment techniques in pelvic radiotherapy. Pelvic IGRT has several general IGRT issues to consider (such as choice of match strategy, prioritisation between multiple treatment targets and margin estimates) as well as issues specific to pelvic radiotherapy, in particular large inter-fraction organ variation. A range of interventions, including adaptive treatment strategies, have been developed to address these challenges. This review covers general considerations for the clinical implementation of pelvic IGRT in routine practice and provides an overview of current knowledge regarding pelvic inter-fraction organ motion. Published IGRT evidence for each of the major tumour sites (gynaecological, prostate, bladder, rectal and anal cancer) is summarised, as are state-of-the-art adaptive approaches. General recommendations for the implementation of an institutional pelvic IGRT strategy include. •Ensuring consistency between treatment intent and the IGRT approach utilised. •Ensuring minimum national and international IGRT guidance is followed while considering the benefit of daily volumetric IGRT. •Ensuring the appropriate allied health professionals (namely therapy radiographers/radiation therapists) lead on undertaking IGRT. •Ensuring the IGRT workflow procedure is clear and includes an escalation process for difficult set-ups. •Ensuring a robust IGRT service is in place before implementing advanced adaptive approaches.

Impact of an alternate feeding program on broiler breeder pullet behavior, performance, and plasma corticosterone.

Broiler breeders are commonly feed restricted using some variation of skip-a-day feeding to prevent excessive body weight (BW) gain and poor flock uniformity that results in lower production levels. However, the level of feed restriction has increased leading to negative effects on broiler breeder welfare. Research needs to be conducted to evaluate alternative feeding programs to diminish the negative impact of restricted feeding on bird welfare. This research examined pullets that were fed soybean hulls (alternate day feeding, ATD) on the off day of a traditional skip-a-day feeding program in comparison to the standard skip-a-day program (SAD). The 2 dietary feeding treatments each had 3 replicate pens of 210 pullets each and were fed from wk 5 to 21 of age. Nitrogen-corrected true metabolizable energy and digestible amino acid coefficients of soybean hulls were determined. Body weight in the ATD feed program was significantly higher (P < 0.001) than the birds on the SAD feed program until 16 wk of age. Feed allocations for the SAD feeding program was increased at 11 wk of age to achieve similar BW prior to photo stimulation. The ATD feed program significantly improved BW uniformity of the birds for weeks 8, 12, 16, and 20. Hens fed on the SAD feed program had a lower mean egg production than the hens fed on the ATD program. There were significant differences on plasma corticosterone concentrations between the feeding days (24 or 48 h after feeding) in both feed programs. There was a shift in the behavior of the birds with significant differences in the feeding, foraging, and comfort behaviors between the feeding programs on the same feed day. Overall, feeding the ATD females soybean hulls on the off feed day improved the BW uniformity and egg production, but further research will be needed to determine potential differences in nutrient utilization or behavior of the pullets that positively impacted this flock performance.

Provision of Organ at Risk Contouring Guidance in UK Radiotherapy Clinical Trials.

AIMS: Accurate delineation of organs at risk (OAR) is vital to the radiotherapy planning process. Inaccuracies in OAR delineation arising from imprecise anatomical definitions may affect plan optimisation and risk inappropriate dose delivery to normal tissues. The aim of this study was to review the provision of OAR contouring guidance in National Institute of Health Research Clinical Research Network (NIHR CRN) portfolio clinical trials. MATERIALS AND METHODS: The National Radiotherapy Quality Trials Assurance (RTTQA) Group carried out a two-round Delphi assessment to determine which OAR descriptions provided optimal guidance. RESULTS: Eighty-four clinical trials involving radiotherapy quality assurance were identified as either in recruitment or in setup within the NIHR CRN portfolio. Fifty-nine trials mandated OAR contouring. In total there were 412 OAR; 171 were uniquely named; 159 OAR had more than one name associated with a single structure, with the greatest nomenclature variation seen for the femoral head ± neck, the parotid gland, and bowel. The two-round Delphi assessment determined 42 OAR descriptions as providing optimal contouring guidance. CONCLUSIONS: This study identified the need for OAR nomenclature and contouring guidance consistency across clinical trials. In response to this study and in conjunction with the Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group, the RTTQA Group is in collaboration with international partners to provide consensus recommendations for OAR delineation in clinical trials.

Detection of Rickettsia spp. and Bartonella spp. in Ctenocephalides felis fleas from free-ranging crab-eating foxes (Cerdocyon thous).

Fleas are insects with a worldwide distribution that have been implicated in the transmission of several pathogens. The present study aimed to investigate the presence of Rickettsia spp. (Rickettsiales: Rickettsiaceae) and Bartonella spp. (Rhizobiales: Bartonellaceae) in fleas from free-ranging crab-eating foxes Cerdocyon thous (Linnaeus, 1766) (Carnivora: Canidae) from Rio Grande do Sul, southern Brazil. Fleas were collected manually from animals and used for the molecular detection of Rickettsia spp. and Bartonella spp. Twenty-nine C. thous were sampled in six municipalities. Four foxes were parasitized by 10 fleas, all of which were identified as Ctenocephalides felis (Bouché, 1935) (Siphonaptera: Pulicidae). DNA from Rickettsia felis Bouyer et al., 2001 and Rickettsia asembonensis Maina et al., 2016 were found in three and eight fleas, respectively. In four fleas, DNA of Bartonella sp. was identified. Phylogenetic analysis grouped Bartonella sp. together with other genotypes previously reported in C. felis worldwide. The scenario described in the present study highlights a Neotropical canid parasitized by the invasive cosmopolitan cat flea, which in turn, is carrying potentially invasive vector-borne microorganisms. These findings suggest that C. felis is adapted to wild hosts in wilderness areas in southern Brazil, hypothetically exposing the Neotropical fauna to unknown ecological and health disturbances.

Biomonitoring Equivalents for cyanide.

Exposure to cyanide is widespread in human populations due to a variety of natural and anthropogenic sources. The potential health risks of excess cyanide exposure are dose-dependent and include effects on the thyroid, the male reproductive system, developmental effects, neuropathies and death. Many organizations have derived exposure guideline values for cyanide, which represent maximum recommended exposure levels for inhalation and oral routes of exposure. Biomonitoring Equivalents (BEs) are estimates of the average biomarker concentrations that correspond to these reference doses. Here, we determine BE values for cyanide. The literature on the pharmacokinetics of cyanide was reviewed to identify a biomarker of exposure. Despite issues with biomarker specificity, thiocyanate (SCN-) in the urine or plasma was identified as the most practical biomarker. BE values were produced that correspond to previously published critical effect levels. These BE values range from 0.0008 to 0.8 mg/L and 0.0005-2.5 mg/L for SCN- in urine and plasma, respectively. Confidence in these BE values varies, depending on route of exposure, biomarker, and health endpoint of interest. We anticipate that these BE values will be useful for lower tier (screening level) chemical risk assessment; however due to issues with biomarker specificity and uncertainty in background levels of SCN-, this approach requires refinement to be useful at higher tiers.

Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency.

PURPOSE: Patients with primary antibody deficiency report poorer quality of life and higher rates of anxiety and depression than the general population. Cognitive-behavioral therapy has been shown to be a valuable treatment for patients with other long-term physical health conditions, improving well-being and enabling them to manage their symptoms more effectively. The aim of this project was to establish the feasibility and effectiveness of providing cognitive-behavioral based therapy to patients with primary antibody deficiency. METHODS: Forty-four patients completed a course of psychological therapy. Participants completed a series of self-report measures examining psychological and physical health, and service usage, prior to starting treatment and following their final session. They also provided feedback on their experience of treatment. RESULTS: Patients showed improvements in anxiety, depression, insomnia and fatigue. There was a high level of acceptability of the service and the potential for long-term cost savings to the NHS. CONCLUSION: Psychological therapy based on the cognitive-behavioral model of treatment appears to be a valuable treatment for patients with primary antibody deficiency and comorbid mental health difficulties.

Identifying characteristic features of the retinal and choroidal vasculature in choroideremia using optical coherence tomography angiography.

PurposeUsing optical coherence tomography angiography (OCTA) to investigate the area with flow in the superficial retinal vessel network (SVRN) and choriocapillaris (CC) layer among male subjects with choroideremia (CHM), female carriers, and normal controls to identify vascular changes.Patients and methodsImages of SRVN and CC layer were acquired in 9 affected males, 5 female carriers, and 14 age- and gender-matched controls using the Angiovue software of the RTVue XR Avanti.ResultsThe mean age was 33 years for affected male CHM patients (median 30 years), 46 years for female carriers (median 53 years), and 39 years for controls (median 38.5). Mean SRVN area±SD in subjects with CHM was 12.93±2.06 mm2, in carrier subjects 15.36±0.60 mm2, and in controls 15.30±1.35 mm2 (P<0.01). The mean CC area±SD with flow was 6.97±5.26 mm2 in CHM subjects, 21.65±0.17 mm2 in carriers and 21.36±0.76 mm2 in controls (P<0.01). SRVN and CC area with flow showed a negative correlation in CHM subjects with the age (r=-0.86; P<0.003 and r=-0.77; P<0.01, respectively). CC area with flow had a positive correlation with SRVN (r=0.83, P<0.001). Overall, visual acuity had a negative correlation with SRVN and CC area with flow (r=-0.67, P<0.001 and r=-0.57, P<0.002, respectively). CONCLUSIONS: This is the first study to highlight changes in the SRVN in CHM subjects. OCTA detected a reduced area with flow in both retinal and choroidal circulations, and may be a useful tool for monitoring natural history and disease progression in forthcoming clinical trials.

Intended and unintended consequences of abortion law reform: perspectives of abortion experts in Victoria, Australia.

INTRODUCTION: In Victoria, Australia, abortion was decriminalised in October 2008, bringing the law in line with clinical practice and community attitudes. We describe how experts in abortion service provision perceived the intent and subsequent impact of the 2008 Victorian abortion law reform. METHODS: Experts in abortion provision in Victoria were recruited for a qualitative semi-structured interview about the 2008 law reform and its perceived impact, until saturation was reached. Nineteen experts from a range of health care settings and geographic locations were interviewed in 2014/2015. Thematic analysis was conducted to summarise participants' views. RESULTS: Abortion law reform, while a positive event, was perceived to have changed little about the provision of abortion. The views of participants can be categorised into: (1) goals that law reform was intended to address and that have been achieved; (2) intent or hopes of law reform that have not been achieved; (3) unintended consequences; (4) coincidences; and (5) unfinished business. All agreed that law reform had repositioned abortion as a health rather than legal issue, had shifted the power in decision making from doctors to women, and had increased clarity and safety for doctors. However, all described outstanding concerns; limited public provision of surgical abortion; reduced access to abortion after 20 weeks; ongoing stigma; lack of a state-wide strategy for equitable abortion provision; and an unsustainable workforce. CONCLUSION: Law reform, while positive, has failed to address a number of significant issues in abortion service provision, and may have even resulted in a 'lull' in action.

The zebrafish eye-a paradigm for investigating human ocular genetics.

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future.