An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma.

BACKGROUND: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. MATERIALS AND METHODS: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). RESULTS: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. CONCLUSIONS: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.

Rapid review: Guides and frameworks to inform planetary health education for health professions.

ISSUE ADDRESSED: Human actions have led to a range of global environmental changes. Health professionals must be prepared to deliver systemic changes to mitigate and adapt to the ecological crisis. This rapid review aimed to describe exemplar frameworks that inform planetary health education across health professions. METHODS: The rapid review methodology was informed by a scoping review process. A targeted search strategy was conducted using one representative database and additional strategies such as expert consultation and citation searching were used. Results are described narratively. RESULTS: Of the 11 637 articles, 17 were eligible for inclusion. The frameworks differed, with many recently developed for health professions broadly using a range of methodologies, including qualitative research, opinion/consensus data, literature reviews, and adaptation of previous models. Models such as metric-based scoring indicators and Sustainable Quality Improvement were featured in the frameworks, as were the application of First Nations Natural Laws. CONCLUSION: This rapid review identifies and showcases accessible, interdisciplinary frameworks to inform the integration of planetary health in curricula, highlighting a rapidly evolving field through which interdisciplinary collaborations in healthcare are important to inform its pedagogy and application. Health education is an important component of health promotion; and thus this rapid review offers a range of approaches that health professionals, health promotion practitioners, and educators can use to inform the integration of planetary health, including sustainable healthcare, into curricula. SO WHAT?: Educational frameworks are informed by research and practice and provide key guidance to practitioners and educators; summarising key available planetary health education frameworks consolidates and guides effective education and builds on the existing body of knowledge to support urgent pro-environmental change.

Neuromodulatory control of inhibitory network arborization in the developing postnatal neocortex.

Interregional neuronal communication is pivotal to instructing and adjusting cortical circuit assembly. Subcortical neuromodulatory systems project long-range axons to the cortex and affect cortical processing. However, their roles and signaling mechanisms in cortical wiring remain poorly understood. Here, we explored whether and how the cholinergic system regulates inhibitory axonal ramification of neocortical chandelier cells (ChCs), which control spike generation by innervating axon initial segments of pyramidal neurons. We found that acetylcholine (ACh) signaling through nicotinic ACh receptors (nAChRs) and downstream T-type voltage-dependent calcium (Ca2+) channels cell-autonomously controls axonal arborization in developing ChCs through regulating filopodia initiation. This signaling axis shapes the basal Ca2+ level range in varicosities where filopodia originate. Furthermore, the normal development of ChC axonal arbors requires proper levels of activity in subcortical cholinergic neurons. Thus, the cholinergic system regulates inhibitory network arborization in the developing neocortex and may tune cortical circuit properties depending on early-life experiences.

Dysregulation of the mesoprefrontal dopamine circuit mediates an early-life stress-induced synaptic imbalance in the prefrontal cortex.

Stress adversely affects an array of cognitive functions. Although stress-related disorders are often addressed in adulthood, far less is known about how early-life stress (ELS) affects the developing brain in early postnatal periods. Here we show that ELS, induced by maternal separation, leads to synaptic alteration of layer 2/3 pyramidal neurons in the prefrontal cortex (PFC) of mice. We find that layer 2/3 neurons show increased excitatory synapse numbers following ELS and that this is accompanied by hyperexcitability of PFC-projecting dopamine (DA) neurons in the ventral tegmental area. Notably, excitatory synaptic change requires local signaling through DA D2 receptors. In vivo pharmacological treatment with a D2 receptor agonist in the PFC of control mice mimics the effects of ELS on synaptic alterations. Our findings reveal a neuromodulatory mechanism underlying ELS-induced PFC dysfunction, and this mechanism may facilitate a more comprehensive understanding of how ELS leads to mental disorders.

A retrospective case-control cohort analysis of comorbidity and health expenditure in hospitalized adults diagnosed with obesity utilizing ICD-10 diagnostic coding.

The cost and comorbidity of obesity in hospitalized inpatients, is less known. A retrospective study of patients presenting to a large district hospital in Western Sydney (April 2016-February 2017) using clinical, pathological as well as diagnostic coding data for obesity as per ICD-10. Of 43 212 consecutive hospital presentations, 390 had an obesity-coded diagnosis (Ob, 0.90%), of which 244 were gender and age-matched to a non-obesity coded cohort (NOb). Weight and BMI were higher in the Ob vs NOb group (126 ± 37 vs 82 ± 25 kg; BMI 46 ± 12 vs 29 ± 8 kg/m2 , P < .001) with a medical record documentation rate of 62% for obesity among Ob. The Ob cohort had 2-5× higher rates of cardiopulmonary and metabolic complications (P < .001), greater pharmacologic burden, length of stay (LOS, 225 vs 89 hours, P < .001) and stay in intensive care but no differences in the prevalence of mental disorders. Compared with BMI <35 kg/m2 , inpatients with BMI >35 kg/m2 were 5× more likely to require intensive care (OR 5.08 [1.43-27.3, 95% CI], P = .0047). The initiation of obesity-specific interventions by clinical teams was very low. People with obesity who are admitted to hospital carry significant cost and complications, yet obesity is seldom recognized as a clinical entity or contributor.

Quantitative proteomic profiling of shake flask versus bioreactor growth reveals distinct responses of Agrobacterium tumefaciens for preparation in molecular pharming.

The preparation of Agrobacterium tumefaciens cultures with strains encoding proteins intended for therapeutic or industrial purposes is an important activity prior to treatment of plants for transient expression of valuable protein products. The rising demand for biologic products such as these underscores the expansion of molecular pharming and warrants the need to produce transformed plants at an industrial scale. This requires large quantities of A. tumefaciens culture, which is challenging using traditional growth methods (e.g., shake flask). To overcome this limitation, we investigate the use of bioreactors as an alternative to shake flasks to meet production demands. Here, we observe differences in bacterial growth among the tested parameters and define conditions for consistent bacterial culturing between shake flask and bioreactor. Quantitative proteomic profiling of cultures from each growth condition defines unique growth-specific responses in bacterial protein abundance and highlights the functional roles of these proteins, which may influence bacterial processes important for effective agroinfiltration and transformation. Overall, our study establishes and optimizes comparable growth conditions for shake flask versus bioreactors and provides novel insights into fundamental biological processes of A. tumefaciens influenced by such growth conditions.

Exposure of Agrobacterium tumefaciens to agroinfiltration medium demonstrates cellular remodelling and may promote enhanced adaptability for molecular pharming.

Agroinfiltration is used to treat plants with modified strains of Agrobacterium tumefaciens for the purpose of transient in planta expression of genes transferred from the bacterium. These genes encode valuable recombinant proteins for therapeutic or industrial applications. Treatment of large quantities of plants for industrial-scale protein production exposes bacteria (harboring genes of interest) to agroinfiltration medium that is devoid of nutrients and carbon sources for prolonged periods of time (possibly upwards of 24 h). Such conditions may negatively influence bacterial viability, infectivity of plant cells, and target protein production. Here, we explored the role of timing in bacterial culture preparation for agroinfiltration using mass spectrometry-based proteomics to define changes in cellular processes. We observed distinct profiles associated with bacterial treatment conditions and exposure timing, including significant changes in proteins involved in pathogenesis, motility, and nutrient acquisition systems as the bacteria adapt to the new environment. These data suggest a progression towards increased cellular remodelling over time. In addition, we described changes in growth- and environment-specific processes over time, underscoring the interconnectivity of pathogenesis and chemotaxis-associated proteins with transport and metabolism. Overall, our results have important implications for the production of transiently expressed target protein products, as prolonged exposure to agroinfiltration medium suggests remodelling of the bacterial proteins towards enhanced infection of plant cells.

Deletion of NRXN1α impairs long-range and local connectivity in amygdala fear circuit.

Neurexins are a family of presynaptic cell adhesion proteins that regulate synaptic structure and maintain normal synaptic transmission. Mutations in the α-isoform of neurexin1-gene (NRXN1α) are linked with cognitive and emotional dysregulation, which are heavily dependent on the amygdala and medial prefrontal cortex (mPFC). It is however not known whether deletion of NRXN1α gene affect specific synaptic elements within the amygdala microcircuit and connectivity with mPFC. In this study, we show that NRXN1α deletion impairs synaptic transmission between the dorsal medial prefrontal cortex (dmPFC) and basal amygdala (BA) principal neurons. Stimulation of dmPFC fibers resulted in reduced paired pulse ratio (PPR) and AMPA/NMDA ratio at dmPFC to BA synapses in NRXN1α-knockout (KO) (NRXN1α KO) mice suggestive of pre- and postsynaptic deficits but there was no change at the lateral amygdala (LA) to BA synapses following LA stimulation. However, feedforward inhibition from either pathway was significantly reduced, suggestive of input-independent deficit in GABAergic transmission within BA. We further analyzed BA inhibitory network and found reduced connectivity between BA GABAergic and glutamatergic neurons in NRXN1α KO mice. As this circuit is tightly linked with fear regulation, we subjected NRXN1α KO and WT mice to discriminative fear conditioning and found a deficit in fear memory retrieval in NRXN1α KO mice compared with WT mice. Together, we provide novel evidence that deletion of NRNX1α disrupts amygdala fear circuit.

History of concussion is associated with higher head acceleration and reduced cervical muscle activity during simulated rugby tackle: An exploratory study.

OBJECTIVES: The objective of this study is to explore the effect of concussion history on head control during front on rugby tackles in non-professional male and female Rugby Union players. DESIGN: An observational cross-sectional design. SETTING: A laboratory-based study of simulated front on rugby tackles with a dynamic relatively-weighted (∼50% body-mass) tackle bag. PARTICIPANTS: 27 club Rugby Union players were recruited; 10 (7female) with no-concussion history, 10 (3female) within 12-months of concussion and 7 (3female) with 24 + months since last concussion. MAIN OUTCOME MEASURES: Linear and rotational head acceleration measured with a skin mounted CSx® triaxial accelerometer. Normalized Surface EMG amplitude of the bilateral sternocleidomastoid (Scm), upper trapezius (Trap) and splenius capitis (Spl). All outcome measures were synchronised with moment of impact with the tackle bag. RESULTS: A mixed-model analysis showed that players with 12-Month concussion history had the highest head acceleration (females = 48.6g, males = 68.3g, p < 0.05) with lower Trap (6.9-11.7%, p < 0.05) and Spl (3-12%, p < 0.05) amplitudes compared to athletes with No-concussion. CONCLUSIONS: These findings suggest probable disruption to neuromuscular control of the head in athletes with concussion history as a potential mechanism for recurrent concussion incidence.

Tranexamic acid toxicity in human periarticular tissues.

OBJECTIVES: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. METHODS: Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. RESULTS: There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. CONCLUSION: The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11-18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1.

Statistical modelling of groundwater contamination monitoring data: A comparison of spatial and spatiotemporal methods.

Field monitoring of groundwater contamination plumes is an important component of managing risks for downgradient receptors and remedial strategies that rely on monitored natural attenuation. Collection of groundwater quality data can however take a considerable effort and be associated with high cost. Here, we investigated the relative merits of analyzing groundwater quality data using spatial compared to spatiotemporal statistical modelling and assessed the accuracy of both methods and implications for data collection requirements. The aim of this was to determine whether the quantity of data collected can be reduced, while retaining the same level of estimation accuracy, by analyzing groundwater contamination data using a spatiotemporal model which "borrows strength" across time, rather than a spatial model for individual sampling events. To capture the variability encountered under field conditions, we used three hypothetical groundwater contamination plumes with increasing complexity, and site data for a large groundwater gasoline additive plume. The results show that spatiotemporal methods can increase efficiency markedly so that, in comparison with repeated spatial analysis, spatiotemporal methods can achieve the same level of performance but with smaller sample sizes.

Two-Photon Bidirectional Control and Imaging of Neuronal Excitability with High Spatial Resolution In Vivo.

Sensory information is encoded within the brain in distributed spatiotemporal patterns of neuronal activity. Understanding how these patterns influence behavior requires a method to measure and to bidirectionally perturb with high spatial resolution the activity of the multiple neuronal cell types engaged in sensory processing. Here, we combined two-photon holography to stimulate neurons expressing blue light-sensitive opsins (ChR2 and GtACR2) with two-photon imaging of the red-shifted indicator jRCaMP1a in the mouse neocortex in vivo. We demonstrate efficient control of neural excitability across cell types and layers with holographic stimulation and improved spatial resolution by opsin somatic targeting. Moreover, we performed simultaneous two-photon imaging of jRCaMP1a and bidirectional two-photon manipulation of cellular activity with negligible effect of the imaging beam on opsin excitation. This all-optical approach represents a powerful tool to causally dissect how activity patterns in specified ensembles of neurons determine brain function and animal behavior.

Multi-centre phase IV trial to investigate the immunogenicity of a new liquid formulation of recombinant human growth hormone in adults with growth hormone deficiency.

PURPOSE: To investigate whether a new liquid formulation of recombinant human growth hormone (r-hGH) induces the production of binding antibodies (BAbs) in adults with congenital or adult-onset growth hormone deficiency (GHD). METHODS: Men or women aged 19-65 years with adult growth hormone deficiency who were r-hGH-naïve or had stopped treatment ≥ 1 month before screening were treated with between 0.15 and 0.30 mg/day r-hGH liquid formulation for 39 weeks. The primary endpoint was the proportion of patients who developed BAbs at any time. Secondary endpoints were the proportion of patients with BAbs who became positive for neutralising antibodies, the effects on biomarkers of r-hGH exposure, safety, and adherence to treatment downloaded from the easypod™ connect software. RESULTS: Seventy-eight patients (61.5% men) with mean age 44.5 years (range 21-65) started and 68 (87.2%) completed the 39-week treatment period. 82.1% were treatment naïve; all were negative for BAbs to r-hGH at baseline. The median (interquartile range) duration of treatment [273 (267.0-277.0) days] was consistent with patients receiving the required doses, and mean treatment adherence measured using easypod™ connect was 89.3%. The proportion of patients who developed BAbs was 0% (95% confidence interval 0-4.68%) and biomarker profiles were consistent with exposure to r-hGH. 92.3% of patients reported ≥ 1 adverse event during treatment. Most events were mild or moderate and no new safety concerns were detected. CONCLUSIONS: The low immunogenicity profile of the liquid formulation was consistent with that for the freeze-dried formulation, and no new safety concerns were reported.

The annual marine feeding aggregation of Atlantic sturgeon Acipenser oxyrinchus in the inner Bay of Fundy: population characteristics and movement.

Atlantic sturgeon Acipenser oxyrinchus aggregate to feed from May to October in Minas Basin (45° N; 64° W), a large, cul-de-sac embayment of the inner Bay of Fundy. The aggregation consists mainly of migrants from the Saint John, NB and Kennebec Rivers, ME (99%). During 2004-2015, 4393 A. oxyrinchus were taken as by-catch by commercial fish trawlers or at intertidal fishing weirs, and 1453 were marked and/or sampled and released. Fork length (LF ) ranged from 458 to 2670 mm, but 72·5% were <1500 mm. Mass (M) ranged from 0·5 to 58·0 kg. The mass-length relationship for fish ≤50 kg was log10 M = 3·32log10 LF - 5·71. Observed growth of unsexed A. oxyrinchus recaptured after 1-8 years indicated fish of 90-179 cm LF grew c. 2-4 cm a year. Ages obtained from pectoral spines were from 4 to 54 years. The Von Bertalanffy growth model predicted K = 0·01 and L∞ = 5209 mm LF . Estimated annual mortality was 9·5-10·9%. Aggregation sizes in 2008 and 2013 were 8804 and 9244 individuals, respectively. Fish exhibited high fidelity for yearly return to Minas Basin and population estimates indicated the total at-sea number utilizing the Basin increased from c. 10 700 in 2010 to c. 37 500 in 2015. Abundance in the Basin was greatest along the north shore in spring and along the south shore in summer, suggesting clockwise movement following the residual current structure. Marked individuals were recaptured in other bays of the inner Bay of Fundy, north to Gaspé, Quebec, and south to New Jersey, U.S.A., with 26 recoveries from the Saint John River, NB, spawning run. Fish marked at other Canadian and U.S. sites were also recovered in Minas Basin. Since all A. oxyrinchus migrate into and out of the Basin annually they will be at risk of mortality if planned tidal power turbines are installed in Minas Passage.

Impact of granulocyte colony-stimulating factors in metastatic colorectal cancer patients.

BACKGROUND: Delays in chemotherapy because of neutropenia may be associated with poorer outcomes. The purpose of the present study was to examine the effect that granulocyte colony-stimulating factors (g-csfs) have on survival. METHODS: We conducted a chart review of all outpatients diagnosed with metastatic colorectal cancer and treated with folfiri chemotherapy (irinotecan, 5-fluorouracil, leucovorin) with or without bevacizumab at Mount Sinai Hospital between 2007 and 2012. Multivariable Cox proportional hazards models were used to compare survival in neutropenic patients treated with g-csf, in neutropenic patients not so treated, and in patients without neutropenia. RESULTS: The review identified 93 patients, 31 of whom did not experience a neutropenic event. Of the 62 who experienced neutropenia, 18 were managed with g-csf support, and 44, with reductions or delays in dose. Compared with patients experiencing a neutropenic episode not treated with g-csf, those treated with g-csf experienced a nonsignificant increase in time to event [progression or death: hazard ratio (hr): 1.37; 95% confidence limits (cl): 0.72, 2.61], but compared with patients not having a neutropenic episode, the same patients experienced a significant increase in time to event (hr: 2.07; 95% cl: 1.03, 4.15). CONCLUSIONS: In patients who experienced neutropenia, g-csf did not have a statistically significant impact on survival. Time to event was prolonged in g-csf-treated patients compared with patients who did not experience neutropenia.

Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression: a marker of malignant potential?

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has a diverse functional repertoire, involved in the innate immune response as well as cell growth and differentiation. Expression has been linked to malignant disease development and progression. METHODS: Neutrophil gelatinase-associated lipocalin expression was assessed immunohistochemically in 98 colorectal neoplastic lesions (52 cancer polyps (CaPs) and 46 sporadic adenoma/adjacent normal mucosa paired specimens) to investigate association with adenoma progression and early colorectal carcinogenesis. RESULTS: Within CaPs, all adenomatous and carcinomatous epithelium expressed NGAL, with 92% (43 out of 47) and 58% (19 out of 33) epithelial positivity, respectively, as well as positive stromal cell expression. This was significantly increased compared with normal mucosal epithelium (P=0.0001). Neutrophil gelatinase-associated lipocalin positivity was also identified in sporadic low-grade adenomas, in both the epithelial and stromal compartments as compared with adjacent normal mucosa (P=0.0001 and 0.0002), and this increased along with adenoma size >1 cm (P=0.03). CONCLUSION: Neutrophil gelatinase-associated lipocalin is expressed by the majority of human neoplastic colorectal lesions. This phenotypic switch occurs at an early stage in neoplastic progression with clear differential expression between normal mucosa and adenomatous polyps, rather than further downstream in disease progression at the adenoma-carcinoma transformation. Thus, NGAL expression is not a useful biomarker for determining disease progression from adenomatous to malignant colorectal neoplasia.

3T diffusion-weighted MRI of the thyroid gland with reduced distortion: preliminary results.

OBJECTIVE: Single-shot diffusion-weighted (DW) echo planar imaging (EPI), which is commonly used for imaging the thyroid, is characterised by severe blurring and distortion. The objectives of this work were: 1, to show that a reduced-field of view (r-FOV) DW EPI technique can improve image quality; and 2, to investigate the effect of different reconstruction strategies on the resulting apparent diffusion coefficients (ADCs). METHODS: We implemented a single-shot, r-FOV DW EPI technique with a two-dimensional radiofrequency excitation pulse for DW imaging of the thyroid at 3T. Images were reconstructed using root sum of squares (SOS) and an optimal-B1 reconstruction (OBR). Phantom and in vivo experiments were performed to compare r-FOV and conventional full-FOV DW EPI with root SOS and OBR. RESULTS: r-FOV with OBR substantially improved image quality at 3T. In phantoms, r-FOV gave more accurate ADCs than full-FOV. In vivo r-FOV always gave lower ADC values with respect to the full-FOV technique irrespective of the reconstruction used and whether only two or multiple b-values were used to compute the ADCs. CONCLUSION: r-FOV DW EPI can reduce image blurring and distortion at the expense of a low signal-to-noise ratio. OBR is a promising reconstruction technique for accurate ADC measurements in lower signal-to-noise ratio regimes, although further studies are needed to characterise its performance. ADVANCES IN KNOWLEDGE: DW imaging of the thyroid at 3T could potentially benefit from r-FOV acquisition strategies, such as the r-FOV DW EPI technique proposed in this paper.

Developing research in partnership with Aboriginal communities - strategies for improving recruitment and retention.

CONTEXT: Australian Aboriginal communities in urban, rural and remote areas are continuing to suffer high rates of perinatal mortality and morbidity that will impact on the future health of the community. It has been well documented that Aboriginal women have extreme distrust of mainstream pregnancy-related health care and suggested that late entry into antenatal care is as high as 50% in the Aboriginal population. Although medical and midwifery staff have long discussed strategies to improve uptake of antenatal health care for Aboriginal women, researchers in many areas have found the recruitment of Aboriginal people into scientific studies almost impossible. This article seeks to share the strategies that have been developed over a period of time by the authors that have proved useful for recruitment and retention into research. It is anticipated that these strategies would also apply for health practitioners in maintaining their patients for clinical care management. ISSUE: Although each research location (regional, rural and remote) has had to spend time determining what approach is best for meeting the research outcomes, many of these suggestions become applicable to clinicians seeking to develop better connections with Aboriginal patients in their clinics. With the management of ongoing chronic health conditions for Aboriginal people a priority in 'Closing the Gap', a number of these suggestions could easily be implemented by clinicians. Remembering that each community has specific needs that must be addressed, priorities for assistance for that community will be easily identifiable after community consultation (eg transport, or ability to access medical testing). Opportunities for the use of new social media (eg Facebook) as communication tools for researchers and clinicians will have increasing applicability as further software updates are created. LESSONS LEARNT: With open and trusting dialogues between researchers, clinicians and Aboriginal communities, we can go a long way towards understanding the needs of individual communities and working in partnerships to close the gap.

Male quality, signal reliability and female choice: assessing the expectations of inter-sexual selection.

Numerous models have attempted to explain the evolution of extravagant male ornaments found in many species. Inter-sexual indicator models postulate that male ornaments evolved as signals of quality, and that females use these signals to select the highest quality males. These models involve three traits--male quality, male signals and female preferences--and have specific expectations about the relative strengths of the phenotypic relationships between these traits. Using data from anuran species, we assessed the relative strengths of the phenotypic relationships using meta-analysis. The relative strengths of these phenotypic correlations were as expected by indicator models, providing support for indicator models of inter-sexual selection. We also found much variation in our data, suggesting that additional, untested factors may mediate inter-sexual interactions in this taxon, such as differences in the importance of quality signalling between species. These factors require investigation, in order to improve our understanding of inter-sexual selection.