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Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 -8 ) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 -6 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1 ) (P=3.15x10 -15 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP ) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6 ), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes., Competing Interests: Competing interests: The following authors report potential competing interests: L.V.W.: Louise V. Wain has received grant support from GSK. M.D.T.: Martin D. Tobin has received grant support from GSK. I.P.H.: Ian P. Hall has received support from GSK and BI., (Copyright: © 2021 Fawcett KA et al.)

The first 5 years of a child's life are crucial in laying the foundation for their health and developmental trajectory into adulthood. These early years are especially influenced by the surrounding environments in which children live and grow. A large international body of evidence demonstrates that children who experience disadvantage tend to fall increasingly behind over time. At the societal level, these inequities can cause substantial social burdens and significant costs across health, education, and welfare budgets. A contributing factor is that children experiencing adversity are less likely to have access to the environmental conditions that support them to thrive. Many of these factors are modifiable at the community or place level. We argue for three key-though not exhaustive-ideas that collectively could achieve more equitable outcomes for children facing disadvantage and experiencing adversity:We conclude that if adopted, these 3 ideas could contribute to the ability of local communities and networks to identify and respond to factors that address early childhood inequalities., (Copyright © 2021. Published by Elsevier Inc.)

Background: Surgical treatment of posterolateral rotatory instability (PLRI) using primary repair or reconstruction of the lateral collateral ligament complex have proven inconsistent. This study aimed to test the hypothesis that augmentation of LUCL repair or palmaris longus tendon reconstruction using a suture tape augmentation would be associated with less rotational displacement and greater torque load to failure (LTF) compared with nonaugmented constructs., Methods: Cadaveric elbows (n = 12 matched pairs) were used. Baseline stiffness and displacement values were obtained. The LUCL was transected followed by repair alone, repair with augmentation, reconstruction with palmaris longus graft, or reconstruction with augmentation. Specimens were retested including torque LTF. Paired t tests were performed to assess the biomechanical effects of augmentation., Results: Augmentation was associated with higher LTF than repair and reconstruction alone ( P  = .008 and .047, respectively). Displacement was less with augmentation in reconstruction groups ( P  = .048) but not in repair groups. Suture tape augmentation maintained rotational stiffness better than repair alone ( P  = .01). Although reconstruction with augmentation maintained rotational stiffness better than nonaugmented reconstruction, the differences were not statistically significant ( P  = .057). Mode of failure for repair alone was predominantly suture pulling through repaired ligament. Augmented repairs primarily failed at the anchor-bone interface. Modes of failure for both reconstruction groups were similar, including graft tearing and/or slipping at the anchor., Conclusion: When positioned in neutral forearm rotation and 90 o of flexion to simulate postoperative conditions, augmentation of LUCL repair or tendon reconstruction using suture tape is associated with better resistance to rotational loads compared with nonaugmented repair or reconstruction, while maintaining near-native rotational stiffness., (© 2020 The Authors.)

Background: Current international consensus is that 'early' referral to palliative care services improves cancer patient and family carer outcomes; however, in practice, these referrals are not routine. Uncertainty about the 'best time' to refer has been highlighted as contributing to care variation. Previous work has identified clear disease-specific transition points in the cancer illness which heralded subsequent poor prognosis (less than 6 months) and which, we contest, represent times when palliative care should be routinely introduced as a standardised approach, if not already in place, to maximise patient and carer benefit. This protocol details a trial that will test the feasibility of a novel standardised outpatient model of early palliative care [Standardised Early Palliative Care (STEP Care)] for advanced cancer patients and their family carers, with referrals occurring at the defined disease-specific evidence-based transition points.The aims of this study are to (1) determine the feasibility of conducting a definitive phase 3 randomised trial, which evaluates effectiveness of STEP Care (compared to usual best practice cancer care) for patients with advanced breast or prostate cancer or high grade glioma; (2) examine preliminary efficacy of STEP Care on patient/family caregiver outcomes, including quality of life, mood, symptoms, illness understanding and overall survival; (3) document the impact of STEP Care on quality of end-of-life care; and (4) evaluate the timing of palliative care introduction according to patients, families and health care professionals., Methods: Phase 2, multicenter, open-label, parallel-arm, randomised controlled trial (RCT) of STEP Care plus standard best practice cancer care versus standard best practice cancer care alone., Discussion: The research will test the feasibility of standardised palliative care introduction based on illness transitions and provide guidance on subsequent development of phase 3 studies of integration. This will directly address the current uncertainty about palliative care timing., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000534381., Competing Interests: Central ethical approval for the trial conduct at all participating sites was provided by the Human Research Ethics Committee at St Vincent’s Hospital Melbourne [HREC 179/16].Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The development of Deep Vein Thrombosis (DVT) is a major concern following orthopaedic surgery. No study has yet to compare the rate and risk factors for DVT between total joint and orthopaedic trauma patients. To evaluate if DVT prophylaxis for trauma should differ from total joints, we explored the rate and risk factors for DVT between both cohorts., Methods: Using a CPT code search from 2005 to 2013 in the ACS-NSQIP database, 150,657 orthopaedic total joint patients and 44,594 orthopaedic trauma patients were identified. DVT complications, patient demographics, preoperative comorbidities, and surgical characteristics were collected for each patient. A chi-squared test was used to compare the risk factors for DVT between orthopaedic trauma and total joint patients. A multivariable logistic regression model was built to adjust for comorbidities for each cohort., Results: The rate of DVT diagnosis in the total joint population was 0.8% (N = 1186) and 0.98% (N = 432) in the orthopaedic trauma population (p = 0.57). After controlling for individual comorbidities, dyspnea, peripheral vascular disease, and renal failure were significant risk factors for DVT in total joint patients (p < 0.05), whereas age, ascites and steroid use were significant risk factors for DVT in orthopaedic trauma patients (p < 0.05)., Conclusions: Historically, the risks for DVT in total joints have been emphasized, yet based on our results, the incidence of DVT is the same for orthopaedic trauma. However, the risk factors varied. It is therefore important to consider specialty-specific DVT prophylaxis for orthopaedic trauma patients in order to improve care and reduce postoperative complications.

Objectives: Despite their public health importance, little is known about associations between modifiable lifestyles, quality of life (QOL), and psychiatric symptoms in men. We investigated relationships between QOL, obesity, mobility and lifestyle in Australian men, including whether associations were mediated by anxiety and depression., Study Design: A cross-sectional study of 893 men (aged 24-92 yrs) participating in the Geelong Osteoporosis Study: an age-stratified, population-based sample of men randomly recruited from the Barwon Statistical Division (BSD), in south-eastern Australia., Main Outcome Measures: Using a validated tool, QOL was measured in the domains of physical health, psychological health, social relationships and the environment. Anxiety and depression were ascertained using the Hospital Anxiety and Depressive Scale. Models were adjusted for age, clinical measures of obesity and mobility, and self-reported lifestyles, with adjustment made for anxiety and depression., Results: Associations were observed between low mobility and lower psychological-related QOL (OR 0.70, 95%CI 0.53-0.93), and for smoking and low mobility with lower environment-related QOL (OR 0.48, 95%CI 0.27-0.84; OR 0.67, 95%CI 0.50-0.90, respectively). Age, anxiety and depression were independently associated with QOL in each domain., Conclusions: Independent of age, anxiety and depression, smoking and low mobility showed particularly strong effects on the likelihood of men reporting a lower satisfaction with their QOL. This information will inform the design of effective and equitable health policies, the allocation of resources toward unmet needs, and the development of strategic health-related plans., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To identify the emergence of the recognition of the potential of the Auger effect for clinical application, and after tracing the salient milestones towards that goal, to evaluate the status quo and future prospects. It was not until 40 years after the discovery of Auger electrons, that the availability of radioactive DNA precursors enabled the biological power, and the clinical potential, of the Auger effect to be appreciated. Important milestones on the path to clinical translation have been identified and reached, but hurdles remain. Nevertheless the potential is still evident, and there is reasonable optimism that the goal of clinical translation is achievable.

Introduction: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture., Methods/results: Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed., Conclusions: Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups., Mini Abstract: Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study examined whether development of two forms of cognitive control (proactive and reactive) between early and midadolescence was associated with the onset of major depressive disorder (MDD) during the same period and if it prospectively predicted MDD onset between mid- and late adolescence. Adolescents (N = 165) completed 3 waves of assessments, at 12 (T1), 16 (T2), and 18 (T3) years of age. Diagnostic interviews were conducted at each time point to identify three groups of adolescents: "early MDD," those who developed MDD between early (T1) and mid- (T2) adolescence (n = 23); "late MDD," those who developed MDD between mid- (T2) and late (T3) adolescence (n = 20); and "controls," those who did not develop MDD (n = 122). A modified Stroop task was completed at T1 and T2 to examine development of proactive and reactive cognitive control. Adolescents with early MDD exhibited significant declines in reactive control, as well as a trend level decline for proactive control, during this period compared to controls. No significant differences in reactive or proactive control were identified in adolescents with late MDD compared to controls, but they did exhibit significant improvements in proactive control compared to those with early MDD. These findings suggest that normative maturation of reactive, and possibly proactive, cognitive control abilities are impaired in adolescents who develop MDD between early and midadolescence. This has implications for understanding the mechanisms underlying certain forms of behavioral dysregulation that are commonly seen in MDD.

Research consistently reports higher rates of problematic drinking among lesbian, bisexual and queer women than among heterosexual women, but relatively little research has identified underlying factors. Within this context, the aim of the present study was to qualitatively explore the sociocultural influences on alcohol consumption among lesbian, bisexual and queer women in Australia. An ethnographic study including in-depth interviews and 10 sessions of participant observation was conducted with 25 Australian lesbian, bisexual and queer women. Analysis of transcripts and fieldnotes focused on lesbian, bisexual and queer-related influences on alcohol consumption. Three lesbian, bisexual and queer-related factors were identified that influenced alcohol use: (1) coping, (2) connection and (3) intersections with lesbian, bisexual and queer identity. Most participants reported consuming alcohol to cope with discrimination or to connect with like-minded others. Alcohol use had positive influences for some women through facilitating social connection and wellbeing. Women with a high lesbian, bisexual and queer identity salience were more likely to seek lesbian, bisexual and queer community connection involving alcohol, to publicly identify as lesbian, bisexual and queer and to experience discrimination. National policies need to address underlying causes of discrimination against lesbian, bisexual and queer women. Alcohol policies and clinical interventions should acknowledge the impact of discrimination on higher alcohol consumption amongst lesbian, bisexual and queer women compared with heterosexual women, and should utilise health promotion messages regarding safe drinking that facilitate lesbian, bisexual and queer social connection.

In this study, we report the epidemiology and risk factors for humeral fractures (proximal humerus and shaft) among men and women residing in south-eastern Australia. Incident fractures during 2006 and 2007 were identified using X-ray reports (Geelong Osteoporosis Study Fracture Grid). Risk factors were identified using data from case-control studies conducted as part of the Geelong Osteoporosis Study. Median age of fracture was lower in males than females for proximal humerus (33.0 vs 71.2 years), but not for humeral shaft (8.9 vs 8.5 years). For females, proximal humerus fractures occurred mainly in the 70-79 and 80+ years age groups, whereas humeral shaft fractures followed a U-shaped pattern. Males showed a U-shaped pattern for both proximal humerus and humeral shaft fractures. Overall age-standardised incidence rates for proximal humerus fractures in males and females were 40.6 (95% CI 32.7, 48.5) and 73.2 (95% CI 62.2, 84.1) per 100,000 person years, respectively. For humeral shaft fractures, the age-standardised rate was 69.3 (95% CI 59.0, 79.6) for males and 61.5 (95% CI 51.9, 71.0) for females. There was an increase in risk of proximal humerus fractures in men with a lower femoral neck BMD, younger age, prior fracture and higher milk consumption. In pre-menopausal women, increased height and falls were both risk factors for proximal humerus fractures. For post-menopausal women, risk factors associated with proximal humerus fractures included a lower non-milk dairy consumption and sustaining a prior fracture. Humeral shaft fractures in both sexes were sustained mainly in childhood, while proximal humerus fractures were sustained in older adulthood. The overall age-standardised rates of proximal humerus fractures were nearly twice as high in females compared to males, whereas the incidence rates of humeral shaft fractures were similar.

Two pervasive and fundamental impacts of urbanization are the loss and fragmentation of natural habitats. From a genetic perspective, these impacts manifest as reduced genetic diversity and ultimately reduced genetic viability. The growling grass frog (Litoria raniformis) is listed as vulnerable to extinction in Australia, and endangered in the state of Victoria. Remaining populations of this species in and around the city of Melbourne are threatened by habitat loss, degradation and fragmentation due to urban expansion. We used mitochondrial DNA (mtDNA) and microsatellites to study the genetic structure and diversity of L. raniformis across Melbourne's urban fringe, and also screened four nuclear gene regions (POMC, RAG-1, Rhod and CRYBA1). The mtDNA and nuclear DNA sequences revealed low levels of genetic diversity throughout remnant populations of L. raniformis. However, one of the four regions studied, Cardinia, exhibited relatively high genetic diversity and several unique haplotypes, suggesting this region should be recognized as a separate Management Unit. We discuss the implications of these results for the conservation of L. raniformis in urbanizing landscapes, particularly the potential risks and benefits of translocation, which remains a contentious management approach for this species.

Urban ecosystems have traditionally been considered to be pervious features of our cities. Their hydrological properties have largely been investigated at the landscape scale and in comparison with other urban land use types. However, hydrological properties can vary at smaller scales depending upon changes in soil, surface litter and vegetation components. Management practices can directly and indirectly affect each of these components and the overall habitat complexity, ultimately affecting hydrological processes. This study aims to investigate the influence that habitat components and habitat complexity have upon key hydrological processes and the implications for urban habitat management. Using a network of urban parks and remnant nature reserves in Melbourne, Australia, replicate plots representing three types of habitat complexity were established: low-complexity parks, high-complexity parks, and high-complexity remnants. Saturated soil hydraulic conductivity in low-complexity parks was an order of magnitude lower than that measured in the more complex habitat types, due to fewer soil macropores. Conversely, soil water holding capacity in low-complexity parks was significantly higher compared to the two more complex habitat types. Low-complexity parks would generate runoff during modest precipitation events, whereas high-complexity parks and remnants would be able to absorb the vast majority of rainfall events without generating runoff. Litter layers on the soil surface would absorb most of precipitation events in high-complexity parks and high-complexity remnants. To minimize the incidence of stormwater runoff from urban ecosystems, land managers could incrementally increase the complexity of habitat patches, by increasing canopy density and volume, preserving surface litter and maintaining soil macropore structure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Exotic species dominate many communities; however the functional significance of species' biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

An experimental approach to road mitigation that maximizes inferential power is essential to ensure that mitigation is both ecologically-effective and cost-effective. Here, we set out the need for and standards of using an experimental approach to road mitigation, in order to improve knowledge of the influence of mitigation measures on wildlife populations. We point out two key areas that need to be considered when conducting mitigation experiments. First, researchers need to get involved at the earliest stage of the road or mitigation project to ensure the necessary planning and funds are available for conducting a high quality experiment. Second, experimentation will generate new knowledge about the parameters that influence mitigation effectiveness, which ultimately allows better prediction for future road mitigation projects. We identify seven key questions about mitigation structures (i.e., wildlife crossing structures and fencing) that remain largely or entirely unanswered at the population-level: (1) Does a given crossing structure work? What type and size of crossing structures should we use? (2) How many crossing structures should we build? (3) Is it more effective to install a small number of large-sized crossing structures or a large number of small-sized crossing structures? (4) How much barrier fencing is needed for a given length of road? (5) Do we need funnel fencing to lead animals to crossing structures, and how long does such fencing have to be? (6) How should we manage/manipulate the environment in the area around the crossing structures and fencing? (7) Where should we place crossing structures and barrier fencing? We provide experimental approaches to answering each of them using example Before-After-Control-Impact (BACI) study designs for two stages in the road/mitigation project where researchers may become involved: (1) at the beginning of a road/mitigation project, and (2) after the mitigation has been constructed; highlighting real case studies when available., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Our world is increasingly urbanizing which is highlighting that sustainable cities are essential for maintaining human well-being. This research is one of the first attempts to globally synthesize the effects of urbanization on ecosystem services and how these relate to governance, social development and climate. Three urban vegetation ecosystem services (carbon storage, recreation potential and habitat potential) were quantified for a selection of a hundred cities. Estimates of ecosystem services were obtained from the analysis of satellite imagery and the use of well-known carbon and structural habitat models. We found relationships between ecosystem services, social development, climate and governance, however these varied according to the service studied. Recreation potential was positively related to democracy and negatively related to population. Carbon storage was weakly related to temperature and democracy, while habitat potential was negatively related to democracy. We found that cities under 1 million inhabitants tended to have higher levels of recreation potential than larger cities and that democratic countries have higher recreation potential, especially if located in a continental climate. Carbon storage was higher in full democracies, especially in a continental climate, while habitat potential tended to be higher in authoritarian and hybrid regimes. Similar to other regional or city studies we found that the combination of environment conditions, socioeconomics, demographics and politics determines the provision of ecosystem services. Results from this study showed the existence of environmental injustice in the developing world.

Aims: To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support., Methods: Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation., Results: Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002)., Conclusions: Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The concept of value is central to the practice and science of ecological management and conservation. There is a well-developed body of theory and evidence that explores concepts of value in different ways across different disciplines including philosophy, economics, sociology and psychology. Insight from these disciplines provides a robust and sophisticated platform for considering the role of social values in ecological conservation, management and research. This paper reviews theories of value from these disciplines and discusses practical tools and instruments that can be utilised by researchers and practitioners. A distinction is highlighted between underlying values that shape people's perception of the world (e.g. altruistic or biospheric value orientations), and the values that people assign to things in the world (e.g. natural heritage, money). Evidence from numerous studies has shown that there are multiple pathways between these values and attitudes, beliefs and behaviours relevant to ecological management and conservation. In an age of increasing anthropogenic impacts on natural systems, recognising how and why people value different aspects of ecological systems can allow ecological managers to act to minimise conflict between stakeholders and promote the social acceptability of management activities. A series of practical guidelines are provided to enable social values to be better considered in ecosystem management and research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Treatment of fungal keratitis remains challenging. To date, only the polyenes and azoles are commonly used topically in the management of fungal keratitis. Natamycin, a polyene, is the only antifungal eye drop that is commercially available; the remainder are prepared in-house and are used in an 'off-label' manner. Failure of medical treatment for fungal keratitis is common, hence there is a need for more effective topical antifungal therapy. To increase the antifungal eye drop armamentarium, it is important to investigate the utility of other classes of antifungal agents for topical use. Caspofungin, an echinocandin antifungal agent, could potentially be used to address the existing shortcomings. However, little is known about the usefulness of topically administered caspofungin. This review will briefly explore the incidence, epidemiology and antifungal treatment of fungal keratitis. It will focus primarily on evidence related to the efficacy, safety and practicality of using caspofungin eye drops in fungal keratitis., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Studies of experimental grassland communities have demonstrated that plant diversity can stabilize productivity through species asynchrony, in which decreases in the biomass of some species are compensated for by increases in others. However, it remains unknown whether these findings are relevant to natural ecosystems, especially those for which species diversity is threatened by anthropogenic global change. Here we analyse diversity-stability relationships from 41 grasslands on five continents and examine how these relationships are affected by chronic fertilization, one of the strongest drivers of species loss globally. Unmanipulated communities with more species had greater species asynchrony, resulting in more stable biomass production, generalizing a result from biodiversity experiments to real-world grasslands. However, fertilization weakened the positive effect of diversity on stability. Contrary to expectations, this was not due to species loss after eutrophication but rather to an increase in the temporal variation of productivity in combination with a decrease in species asynchrony in diverse communities. Our results demonstrate separate and synergistic effects of diversity and eutrophication on stability, emphasizing the need to understand how drivers of global change interactively affect the reliable provisioning of ecosystem services in real-world systems.

Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km(2)) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.

Structured decision making and value-of-information analyses can be used to identify robust management strategies even when uncertainty about the response of the system to management is high. We used these methods in a case study of management of the non-native invasive species gray sallow willow (Salix cinerea) in alpine Australia. Establishment of this species is facilitated by wildfire. Managers are charged with developing a management strategy despite extensive uncertainty regarding the frequency of fires, the willow's demography, and the effectiveness of management actions. We worked with managers in Victoria to conduct a formal decision analysis. We used a dynamic model to identify the best management strategy for a range of budgets. We evaluated the robustness of the strategies to uncertainty with value-of-information analyses. Results of the value-of-information analysis indicated that reducing uncertainty would not change which management strategy was identified as the best unless budgets increased substantially. This outcome suggests there would be little value in implementing adaptive management for the problem we analyzed. The value-of-information analyses also highlighted that the main driver of gray sallow willow invasion (i.e., fire frequency) is not necessarily the same factor that is most important for decision making (i.e., willow seed dispersal distance). Value of-information analyses enables managers to better target monitoring and research efforts toward factors critical to making the decision and to assess the need for adaptive management., (©2012 Society for Conservation Biology.)

Urbanization is currently responsible for widespread declines of amphibian populations globally through the loss, isolation, and degradation of habitat. However, it is not clear how urbanization affects amphibian communities at both local (pond) and landscape scales. We assessed the breeding distribution of frogs in ponds along an urban-rural gradient in Greater Melbourne, Australia, and examined community relationships with habitat quality and landscape context. We sampled frog larvae at 65 ponds on four separate occasions and collected data on local pond and landscape variables. Using Bayesian Poisson regression modeling we found that species richness decreased at ponds surrounded by high densities of human residents and at ponds with high water conductivity, whereas species richness increased substantially at ponds surrounded by a high proportion of green open space. Ordination of individual species presence-absence data by canonical correspondence analysis largely confirmed these findings. Ordination also highlighted the negative influences of pond shading and density of predatory fish, and the positive influence of aquatic vegetation, on community composition. Individual species' responses to urbanization varied. Urbanization had strong negative effects on species that were associated with well-vegetated, sunny, fish-free ponds. Our study highlights the importance of strategic management actions in urban landscapes to improve terrestrial habitat and connectivity around ponds and other wetlands, and local management actions to improve water quality, remove predatory fish, and plant aquatic vegetation at breeding sites.

Tree resistance can be enhanced by a variety of biotic and abiotic inducers, including nonpathogenic and pathogenic microbes, and herbivores, resulting in enhanced protection against further biotic injury. Induced resistance (IR) could be a valuable tool in sustainable pest management. IR has been actively studied in herbaceous plant species, and, in recent years, in woody plant species, and is fast emerging as an intriguing, eco-friendly concept for enhancing tree resistance. However, before application of IR becomes possible, there is a need to increase our knowledge of the mechanisms of defence in forest trees. A richer understanding of these phenomena will play a critical role in developing sustainable integrated pest management strategies. This review summarizes our current knowledge of IR in forest trees, focusing on inducible defence mechanisms, systemic induction of resistance and phytohormone signalling networks. We conclude by discussing the potential advantages and limitations of applying IR-based management tools in forest systems.

This study investigated whether obstacle crossing performance differs between the first and subsequent attempts in people recovering from stroke. Thirty two people with stroke performed eight trials stepping over a 4 cm high obstacle. Spatiotemporal measures of gait were captured by a Vicon 3D motion analysis system. Data collected only from those subjects who completed three trials leading with the affected limb or three trials leading with the unaffected limb were analysed. These criteria resulted in data from only 22 subjects being used in the analysis. Repeated measures MANOVA analyses showed no differences in the spatiotemporal data between the first, second or third trials when leading with either the affected (p=.317) or unaffected limb (p=.801). In general, intraclass correlations showed there were moderate to strong correlations for the spatiotemporal data across the trials (.612-.952), with the exception of trail step time (.480). These results show there are no differences between the spatiotemporal data collected in the first, second and third obstacle crossing trials. This suggests data from a single trial can be considered representative of performance in people with stroke.

We report a case of acute chylous peritonitis mimicking acute appendicitis in a man with acute on chronic pancreatitis. Pancreatitis, both acute and chronic, causing the development of acute chylous ascites and peritonitis has rarely been reported in the English literature. This is the fourth published case of acute chylous ascites mimicking acute appendicitis in the literature.

Objective: To investigate scanpath abnormalities during the encoding of static stimuli in schizophrenia and their interaction with visuospatial working memory (VSWM) dysfunction., Methods: Outpatients with schizophrenia and control subjects were asked to encode a static pattern for subsequent recognition after a short delay. We measured the number of correct and incorrect choices. We also assessed the number and the distribution of fixations, the scanning time in specific regions of interest (ROIs) and the head movements during the encoding of the stimuli. The distributions of fixations and scanning time in definite ROIs during the discrimination of the correct pattern from the foils were also measured., Results: Patients recognised fewer correct patterns than controls. Correct trials in patients were characterised by a specific exploration of the central part of the stimulus during its presentation, whereas this feature was absent in incorrect trials. However, the scanning time and the numbers of fixations and head movements during encoding were similar in both groups and unrelated to recognition accuracy. In both groups, correct trials were associated with a selective exploration of the correct pattern amongst the six possibilities during recognition. Furthermore, patients gave more attention to incorrect patterns with a leftmost element identical to that of the correct response and also those approximating its global structure., Conclusion: Patients showed a VSWM deficit independent of oculomotor dysfunctions and head movements during encoding. Patients' correct trials were related to specific scanning during encoding and discrimination phases. Analysis of these patterns suggests that patients try to compensate for reduced VSWM ability by using specific encoding strategies.

Melioidosis, an infection due to the environmental bacterium Burkholderia pseudomallei, is endemic to Southeast Asia and northern Australia, with cases strongly correlated with the monsoonal wet season. We hypothesized that seasonal variation in the mode of acquisition, informed by traditional knowledge, would result in variations in disease characteristics as well as disease incidence. We explored the seasonal variation in acute, culture-confirmed melioidosis using local Aboriginal definitions of seasons in presentations to the Royal Darwin Hospital, the referral centre for the Top End of the Northern Territory, Australia. In 387 patients, we observed an increased proportion of patients with pneumonia (60%) and severe sepsis (25%) associated with presentations in the wet seasons Gunumeleng (October-December) and Gudjewg (January-March) compared with the drier seasons Wurrgeng (June August) and Gurrung (August-October) (pneumonia 26%, severe sepsis 13%). This observation supports the hypothesis that in the wet seasons there may be changes in the mode and/or magnitude of exposure to B. pseudomallei, with a shift from percutaneous inoculation to aerosol inhalation, for instance.

Developing tools to predict the location of new biological invasions is essential if exotic species are to be controlled before they become widespread. Currently, alpine areas in Australia are largely free of exotic plant species but face increasing pressure from invasive species due to global warming and intensified human use. To predict the potential spread of highly invasive orange hawkweed (Hieracium aurantiacum) from existing founder populations on the Bogong High Plains in southern Australia, we developed an expert-based, spatially explicit, dispersal-constrained, habitat suitability model. The model combines a habitat suitability index, developed from disturbance, site wetness, and vegetation community parameters, with a phenomenological dispersal kernel that uses wind direction and observed dispersal distances. After generating risk maps that defined the relative suitability of H. aurantiacum establishment across the study area, we intensively searched several locations to evaluate the model. The highest relative suitability for H. aurantiacum establishment was southeast from the initial infestations. Native tussock grasslands and disturbed areas had high suitability for H. aurantiacum establishment. Extensive field searches failed to detect new populations. Time-step evaluation using the location of populations known in 1998-2000, accurately assigned high relative suitability for locations where H. aurantiacum had established post-2003 (AUC [area under curve] = 0.855 +/- 0.035). This suggests our model has good predictive power and will improve the ability to detect populations and prioritize areas for ongoing monitoring.

Background: The origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progress., Aims: To investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individuals., Method: Participants consisted of two groups: controls (n=17) and individuals at ultra-high risk for development of psychosis (n=16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month interval., Results: Both the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over time., Conclusions: These preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication.

Active adaptive management balances the requirements of management with the need to learn about the system being managed, which leads to better decisions. It is difficult to judge the benefit of management actions that accelerate information gain, relative to the benefit of making the best management decision given what is known at the time. We present a first step in developing methods to optimize management decisions that incorporate both uncertainty and learning via adaptive management. We assumed a manager can allocate effort to discrete units (e.g., areas for revegetation or animals for reintroduction), the outcome can be measured as success or failure (e.g., the revegetation in an area is successful or the animal survives and breeds), and the manager has two possible management options from which to choose. We further assumed that there is an annual budget that may be allocated to one or both of the two options and that the manager must decide on the allocation. We used Bayesian updating of the probability of success of the two options and stochastic dynamic programming to determine the optimal strategy over a specified number of years. The costs, level of certainty about the success of the two options, and the timeframe of management all influenced the optimal allocation of the annual budget. In addition, the choice of management objective had a large influence on the optimal decision. In a case study of Merri Creek, Melbourne, Australia, we applied the approach to determining revegetation strategies. Our approach can be used to determine how best to manage ecological systems in the face of uncertainty.

Falls on stairs, kerbs and footpaths are a major cause of morbidity in older female adults. This investigation examined the stepping responses made by 48 elderly (mean age 67 years, S.D. 5.4 years) and 48 young (mean age 20 years, S.D. 2.4 years) healthy, community-dwelling adult females to approach and accommodate known surface height changes. The surface was designed to simulate an object like a kerb or step in the walking path. For ascent, the surface was 9 m long (height, 15 cm) with a 13 m ground-level approach. For descent, it was 15m long (height, 15 cm) with a 7 m ground-level departure. These tasks (particularly descent) perturbed the gait of the elderly more than the young. The elderly exerted more control or were more cautious. They made earlier and larger step adjustments (p<.05), primarily employed a short step crossing strategy (elderly, 60%; young, 19%), exhibited less footfall variability (p<.05), moved slower across the step (p<.001) and spent more time in double foot support while crossing the step. In descent, the elderly preferred to land on the forefoot (p<.001). In both conditions, the elderly placed the feet closer to the step and cleared it by a lesser margin. Step descent appears to be particularly hazardous for older females since foot clearances were small and foot placement was closer to the step.

Background: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropenia, but its role in the treatment of infection in non-neutropenic hosts is less well defined., Objectives: We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropenic adults., Search Strategy: For this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (1950 to January 2007); EMBASE (1988 to January 2007); and online databases of clinical trials (www.controlled-trials.com, updated 10 November, 2006)., Selection Criteria: We considered randomized controlled trials (RCTs) which included hospitalized adult patients with either community-acquired pneumonia or hospital-acquired pneumonia., Data Collection and Analysis: Two review authors independently extracted data and assessed trial quality. The primary outcome measure was 28-day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study., Main Results: Six studies with a total of 2018 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28-day mortality (pooled OR 0.81; 95% CI: 0.52 to 1.27)., Authors' Conclusions: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

While previous studies have examined how forest management is influenced by the risk of fire, they rely on probabilistic estimates of the occurrence and impacts of fire. However, nonprobabilistic approaches are required for assessing the importance of fire risk when data are poor but risks are appreciable. We explore impacts of fire risk on forest management using as a case study a water catchment in the Australian Capital Territory (ACT) (southeastern Australia). In this forested area, urban water supply and timber yields from exotic plantations are potential joint but also competing land uses. Our analyses were stimulated by extensive wildfires in early 2003 that burned much of the existing exotic pine plantation estate in the water catchment and the resulting need to explore the relative economic benefits of revegetating the catchment with exotic plantations or native vegetation. The current mean fire interval in the ACT is approximately 40 years, making the establishment of a pine plantation economically marginal at a 4% discount rate. However, the relative impact on water yield of revegetation with native species and pines is very uncertain, as is the risk of fire under climate change. We use info-gap decision theory to account for these nonprobabilistic sources of uncertainty, demonstrating that the decision that is most robust to uncertainty is highly sensitive to the cost of native revegetation. If costs of native revegetation are sufficiently small, this option is more robust to uncertainty than revegetation with a commercial pine plantation.

This study investigates the impact of theory of mind (ToM) deficits on poor insight in schizophrenia. The scale for unawareness of mental disorder (SUMD) was administered to 58 stable outpatients with schizophrenia. First and second order false belief tasks, the Eyes test and a battery of nonToM cognitive measures were administered. The Second order false belief task was the best predictor of each global insight and symptom attribution scores of the SUMD. ToM tasks explained the substantial amount of the variance (ranging from 22.5% to 29.9%) for the insight scores and classified the significant amount of the patients who were aware of the illness correctly. WCST perseveration scores did not contribute to insight scores beyond that contributed by second order false belief tasks. The Second order ToM tasks seems to have critical importance for the awareness of the disorder. Beyond more direct self-evaluation, the awareness of the disorder and its consequences may also require the ability to evaluate the self from the perspective of others. "Understanding the others' belief about another person" may be conceptually very similar to "understanding the others' belief about self" (instead of another person).

Context: Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome., Objective: To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses., Design: Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit., Setting: Early psychosis clinic., Participants: Forty-six patients with first-episode psychosis., Main Outcome Measures: We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms., Results: The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome., Conclusions: Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Background: Relatively few studies have examined relationships between the social networks of people with psychotic disorder and other aspects of their functioning. The aim of this paper is to describe the social networks of people with psychosis and to investigate relationships between social networks and personal and occupational functioning, taking account of illness course., Methods: A two-phase epidemiological survey of persons with psychosis was conducted in four predominantly urban areas of Australia. A census and screen for psychosis was followed by a semi-structured interview of a stratified random sample of participants to assess their functioning. Data relating to functioning and social networks from 908 individuals (most with a diagnosis of schizophrenia) were analysed using structural equation modelling (SEM)., Results: The majority of people with psychosis (67 %) had a network comprising of family and friends, 15 % were defined as having a family-dominated network, 11 % a friends-dominated network and 7 % of participants were defined as socially isolated (no family or friends). Participants who had friends and family in their network (12 %) or who had a family-dominated network (7 %) were more likely to be in full-time employment compared with those with a friends-dominated network (4 %) or those who were socially isolated (5 %). Dysfunction in self-care was more frequently reported among socially isolated people (50 %) and those with family-dominated networks (47 %) than among those with friends-dominated networks (35 %) and those who had friends and family in their social network (23 %). SEM revealed a strong association between social integration and functioning (r = 0.71), even after controlling for illness course. Social integration was defined as having contact with family and/or friends and functioning was defined as having employment and no difficulties in self-care. Male gender was associated with poorer self-care, and female gender was slightly, but significantly, associated with a greater likelihood of having friends., Conclusion: There is a strong relationship between social networks and functioning after taking account of course of illness. That is, the presence of family and friends is generally associated with better self-care and employment. Interventions that are targeted at improving social relationships are likely to have a positive impact on self-care and occupational functioning (and vice versa).

Objectives: This paper reviews the use of clinical indicators in a consultation-liaison (C-L) service over a 12-month period at the Royal Melbourne Hospital, Melbourne, Australia., Method: Clinical indicators and C-L data were collected during the 1999 calendar year. A review of the process was conducted during and after completion of the 12-month period., Results: The system was found to be practical and useful. The use of clinical indicators led to the identification of problems and stimulated effective interventions. The use of the clinical indicators was associated with improvement in communication between C-L staff, parent units and practitioners providing follow-up., Conclusions: The implementation of a database and clinical indicators was a useful addition to the C-L service. The use of clinical indicators was effective in improving clinical performance. These benefits need to be balanced against increased administrative burden.