Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG/2GSH and the availability of Cu(I)

Glutaredoxins have been characterised as enzymes regulating the redox status of protein thiols via cofactors GSSG/GSH. However, such a function has not been demonstrated with physiologically relevant protein substrates in in vitro experiments. Their active sites frequently feature a Cys-xx-Cys motif that is predicted not to bind metal ions. Such motifs are also present in copper-transporting proteins such as Atox1, a human cytosolic copper metallo-chaperone. In this work, we present the first demonstration that: (i) human glutaredoxin 1 (hGrx1) efficiently catalyses interchange of the dithiol and disulfide forms of the Cys(12)-xx-Cys(15) fragment in Atox1 but does not act upon the isolated single residue Cys(41); (ii) the direction of catalysis is regulated by the GSSG/2GSH ratio and the availability of Cu(I); (iii) the active site Cys(23)-xx-Cys(26) in hGrx1 can bind Cu(I) tightly with femtomolar affinity (K(D) = 10(-15.5) M) and possesses a reduction potential of E(o)' = -118 mV at pH 7.0. In contrast, the Cys(12)-xx-Cys(15) motif in Atox1 has a higher affinity for Cu(I) (K(D) = 10(-17.4) M) and a more negative potential (E(o)' = -188 mV). These differences may be attributed primarily to the very low pKa of Cys23 in hGrx1 and allow rationalisation of conclusion (ii) above: hGrx1 may catalyse the oxidation of Atox1(dithiol) by GSSG, but not the complementary reduction of the oxidised Atox1(disulfide) by GSH unless Cu(aq)(+) is present at a concentration that allows binding of Cu(I) to reduced Atox1 but not to hGrx1. In fact, in the latter case, the catalytic preferences are reversed. Both Cys residues in the active site of hGrx1 are essential for the high affinity Cu(I) binding but the single Cys(23) residue only is required for the redox catalytic function. The molecular properties of both Atox1 and hGrx1 are consistent with a correlation between copper homeostasis and redox sulfur chemistry, as suggested by recent cell experiments. These proteins appear to have evolved the features necessary to fill multiple roles in redox regulation, Cu(I) buffering and Cu(I) transport.

Web-based alcohol intervention for Māori university students: double-blind, multi-site randomized controlled trial

AIMS: Like many indigenous peoples, New Zealand Māori bear a heavy burden of alcohol-related harm relative to their non-indigenous compatriots, and disparities are greatest among young adults. We tested the effectiveness of web-based alcohol screening and brief intervention (e-SBI) for reducing hazardous drinking among Māori university students. DESIGN: Parallel, double-blind, multi-site, randomized controlled trial. SETTING: Seven of New Zealand's eight universities. PARTICIPANTS: In April 2010, we sent e-mail invitations to all 6697 17-24-year-old Māori students to complete a brief web questionnaire including the Alcohol Use Disorders Identification Test (AUDIT)-C, a screening tool for hazardous and harmful drinking. Those screening positive were computer randomized to: <10 minutes of web-based alcohol assessment and personalized feedback (intervention) or screening alone (control). MEASUREMENTS: We conducted a fully automated 5-month follow-up assessment with observers and participants blinded to study hypotheses, design and intervention delivery. Pre-determined primary outcomes were: (i) frequency of drinking, (ii) amount consumed per typical drinking occasion, (iii) overall volume of alcohol consumed and (iv) academic problems. FINDINGS: Of the participants, 1789 were hazardous or harmful drinkers (AUDIT-C ≥ 4) and were randomized: 850 to control, 939 to intervention. Follow-up assessments were completed by 682 controls (80%) and 733 intervention group members (78%). Relative to controls, participants receiving intervention drank less often [RR = 0.89; 95% confidence interval (CI): 0.82-0.97], less per drinking occasion (RR = 0.92; 95% CI: 0.84-1.00), less overall (RR = 0.78; 95% CI: 0.69-0.89) and had fewer academic problems (RR = 0.81; 95% CI: 0.69-0.95). CONCLUSIONS: Web-based screening and brief intervention reduced hazardous and harmful drinking among non-help-seeking Māori students in a large-scale pragmatic trial. The study has wider implications for behavioural intervention in the important but neglected area of indigenous health.

Avoiding competition? Site use, diet and foraging behaviours in two similarly sized geese wintering in China

Competition may occur when two species with similar feeding ecologies exploit the same limited resources in time and space. In recent years, the Eastern Tundra Bean Goose Anser fabalis serrirostris and Greater White-fronted Goose Anser albifrons frontalis have increased in wintering numbers at Shengjin Lake, China. To examine the potential for coexistence and possible avoidance strategies, we studied (1) their habitat use, (2) foraging behaviours and (3) diets of birds foraging in mixed- and single-species flocks. Both species extensively exploited sedge meadows, where they showed considerable overlap in spatial distribution and diet. The percentage feeding time and diet of both species were unaffected by the presence of the other. Greater White-fronted Geese appeared diurnal sedge meadow specialists, almost never feeding in other habitats. Eastern Tundra Bean Geese were less selective, exploiting other habitats, which they increasingly exploited at night in mid-winter. The use of alternative habitats and night feeding may have avoided interspecific competition. While the specialised feeding ecology of Greater White-fronted Geese may make them particularly vulnerable to loss of sedge meadow habitat, Eastern Tundra Bean Geese may be able to adjust because of their use of alternative habitats and a less restricted diet.

Perspectives of clinical handover processes: a multi-site survey across different health professionals

AIMS AND OBJECTIVES: To examine the perspectives of health professionals of different disciplines about clinical handover. BACKGROUND: Ineffective handovers can cause major problems relating to the lack of delivery of appropriate care. DESIGN: A prospective, cross-sectional design was conducted using a survey about clinical handover practices. METHODS: Health professionals employed in public metropolitan hospitals, public rural hospitals and community health centres were involved. The sample comprised doctors, nurses and allied health professionals, including physiotherapists, social workers, pharmacists, dieticians and midwives employed in Western Australia, New South Wales, South Australia and the Australian Capital Territory. The survey sought information about health professionals' experiences about clinical handover; their perceived effectiveness of clinical handover; involvement of patients and family members; health professionals' ability to confirm understanding and to clarify clinical information; role modelling behaviour of health professionals; training needs; adverse events encountered and possibilities for improvements. RESULTS: In all, 707 health professionals participated (response rate = 14%). Represented professions were nursing (60%), medicine (22%) and allied health (18%). Many health professionals reported being aware of adverse events where they noticed poor handover was a significant cause. Differences existed between health professions in terms of how effectively they gave handover, perceived effectiveness of bedside handover vs. nonbedside handover, patient and family involvement in handover, respondents' confirmation of understanding handover from their perspective, their observation of senior health professionals giving feedback to junior health professionals, awareness of adverse events and severity of adverse events relating to poor handovers. CONCLUSIONS: Complex barriers impeded the conduct of effective handovers, including insufficient opportunities for training, lack of role modelling, and lack of confidence and understanding about handover processes. RELEVANCE TO CLINICAL PRACTICE: Greater focus should be placed on creating opportunities for senior health professionals to act as role models. Sophisticated approaches should be implemented in training and education.

Variation at the DRD4 locus is associated with wariness and local site selection in urban black swans

 BACKGROUND: Interactions between wildlife and humans are increasing. Urban animals are often less wary of humans than their non-urban counterparts, which could be explained by habituation, adaptation or local site selection. Under local site selection, individuals that are less tolerant of humans are less likely to settle in urban areas. However, there is little evidence for such temperament-based site selection, and even less is known about its underlying genetic basis. We tested whether site selection in urban and non-urban habitats by black swans (Cygnus atratus) was associated with polymorphisms in two genes linked to fear in animals, the dopamine receptor D4 (DRD4) and serotonin transporter (SERT) genes.

RESULTS: Wariness in swans was highly repeatable between disturbance events (repeatability = 0.61) and non-urban swans initiated escape from humans earlier than urban swans. We found no inter-individual variation in the SERT gene, but identified five DRD4 genotypes and an association between DRD4 genotype and wariness. Individuals possessing the most common DRD4 genotype were less wary than individuals possessing rarer genotypes. As predicted by the local site selection hypothesis, genotypes associated with wary behaviour were over three times more frequent at the non-urban site. This resulted in moderate population differentiation at DRD4 (FST = 0.080), despite the sites being separated by only 30 km, a short distance for this highly-mobile species. Low population differentiation at neutrally-selected microsatellite loci and the likely occasional migration of swans between the populations reduces the likelihood of local site adaptations.

CONCLUSION: Our results suggest that wariness in swans is partly genetically-determined and that wary swans settle in less-disturbed areas. More generally, our findings suggest that site-specific management strategies may be necessary that consider the temperament of local animals.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders

© 2015 The Royal Australian and New Zealand College of Psychiatrists. Objectives: To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. Methods: Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care. Conclusions: The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. Mood Disorders Committee: Professor Gin Malhi (Chair), Professor Darryl Bassett, Professor Philip Boyce, Professor Richard Bryant, Professor Paul Fitzgerald, Dr Kristina Fritz, Professor Malcolm Hopwood, Dr Bill Lyndon, Professor Roger Mulder, Professor Greg Murray, Professor Richard Porter and Associate Professor Ajeet Singh. International expert advisors: Professor Carlo Altamura, Dr Francesco Colom, Professor Mark George, Professor Guy Goodwin, Professor Roger McIntyre, Dr Roger Ng, Professor John O'Brien, Professor Harold Sackeim, Professor Jan Scott, Dr Nobuhiro Sugiyama, Professor Eduard Vieta, Professor Lakshmi Yatham. Australian and New Zealand expert advisors: Professor Marie-Paule Austin, Professor Michael Berk, Dr Yulisha Byrow, Professor Helen Christensen, Dr Nick De Felice, A/Professor Seetal Dodd, A/Professor Megan Galbally, Dr Josh Geffen, Professor Philip Hazell, A/Professor David Horgan, A/Professor Felice Jacka, Professor Gordon Johnson, Professor Anthony Jorm, Dr Jon-Paul Khoo, Professor Jayashri Kulkarni, Dr Cameron Lacey, Dr Noeline Latt, Professor Florence Levy, A/Professor Andrew Lewis, Professor Colleen Loo, Dr Thomas Mayze, Dr Linton Meagher, Professor Philip Mitchell, Professor Daniel O'Connor, Dr Nick O'Connor, Dr Tim Outhred, Dr Mark Rowe, Dr Narelle Shadbolt, Dr Martien Snellen, Professor John Tiller, Dr Bill Watkins, Dr Raymond Wu.

Effects of the fire regime on mammal occurrence after wildfire: site effects vs landscape context in fire-prone forests

Wildfires have major impacts on ecosystems globally. Fire regimes (including fire frequency, intensity, season and type of fire) influence the status of species by altering habitat suitability at the site scale, and by creating heterogeneity at the landscape scale. The relative effects of site and landscape-scale fire attributes on animal species are rarely examined together. Such knowledge is important, given that fire regimes are sensitive to changing land management practices; and that fires are predicted to become larger and more frequent in some regions as a result of climate change. Here, we tested the relative influence of elements of the fire regime (fire severity, fire history) at the site-scale, and the landscape context (extent of surrounding unburnt forest, fire heterogeneity) on the occurrence of native terrestrial mammals after severe wildfire in south-eastern Australia. We conducted surveys by using automatically triggered, infrared cameras at 80 sites in fire-prone eucalypt forests, 2-3. years post-wildfire. Thirteen native mammal species were recorded, eight of which were detected with sufficient frequency for analysis. Most species were widespread (35-90% of sites) and recorded in all fire severity classes. Fire effects at the site-level were more influential than landscape context effects arising from heterogeneity in the fire regime (e.g. extent of surrounding unburnt forest). Fire severity was the most influential of the fire-regime elements investigated, but it affected different species in different ways. This study highlights three main points relevant to conservation of terrestrial mammals after wildfire. First, spatial variation in fire severity associated with wildfire (ranging from unburned to severely burned stands) is an important contributor to the post-fire status of species. Second, post-fire environmental conditions are significant: here, rapid regeneration of vegetation following drought-breaking rains greatly influenced the suitability of post-fire habitats. Third, it is valuable to consider the effects of the fire regime at multiple scales, including both the site (forest stand) and its landscape context. Insights from short-term surveys, such as this, will be enhanced by complementary longitudinal studies, especially where they encompass environmental variation through the post-fire succession.

Inter-hospital 'patient expect' calls of clinical handovers for expected patients transferred from rural to metropolitan hospitals: a retrospective clinical audit

Patients requiring inter-hospital air transport across large geographical spaces are at significant risk of adverse outcomes. The aims of this study were to examine the characteristics of clinical handover conducted by telephone and subsequently transcribed in medical records during the inter-hospital transfer of rural patients, and to identify any deficits of this telephone clinical handover. A retrospective audit was conducted of transcribed telephone handovers ('patient expect' calls) occurring with inter-hospital transfers from two rural hospitals to a metropolitan tertiary hospital of all rural patients (n = 127) between January and June 2012. Patient transport between various sites occurred through the Royal Flying Doctor Service. For these hospitals, patient expect calls constituted the only handover record for clinicians during the time of patient transport. Information on patient identification stickers relating to patients' age or gender did not always correspond with details collected during patient expect calls. The name of a clinician at the receiving hospital authorising the transfer was provided in 14 calls (11.1%). It was difficult to determine who made and received calls, and who accepted responsibility for patients at the receiving site. Deterioration in a patient's condition was made in three calls. Actions to be taken after patients' arrival were included in 24 (19%) calls. Planning was restricted to identifying who to contact to review instructions. Inconsistent and overuse of abbreviations was likely to have affected the ability to accurately read back patient information. Crucial information was missing from calls, which may have contributed to delayed and inappropriate delivery of care.

Structural health monitoring: a practical approach to achieving in-situ and site-specific warning of pipeline corrosion and coating failure

An approach to achieving the ambitious goal of cost effectively extending the safe operation life of energy pipelines to, for instance, 100 years is the application of structural health monitoring and life prediction tools that are able to provide long-term remnant pipeline life prediction and in-situ pipeline condition monitoring. A critical step in pipeline structural health monitoring is the enhancement of technological capabilities that are required for quantifying the effects of key factors influencing buried pipeline corrosion and environmentally assisted materials degradation, and the development of condition monitoring technologies that are able to provide in-situ monitoring and site-specific warning of pipeline damage. This paper provides an overview of our current research aimed at developing new sensors for monitoring, categorising and quantifying the level and nature of external pipeline and coating damages under the combined effects of various inter-related variables and processes such as localised corrosion, coating damage and disbondment, cathodic shielding. The concept of in-situ monitoring and site-specific warning of pipeline corrosion is illustrated by a case of monitoring localised corrosion under disbonded coatings using a new corrosion monitoring probe. A basic principle that underpins the use of sensors to monitor localised corrosion has been presented: Localised corrosion and coating failure are not an accidental occurrence, it occurs as the result of fundamental thermodynamic instability of a metal exposed to a specific environment. Therefore corrosion and coating disbondment occurring on a pipeline will also occur on a sensor made of the same material and exposed to the same pipeline condition. Although the exact location of localised corrosion or coating disbondment could be difficult to pinpoint along the length of a buried pipeline, the ‘worst-case scenario’ and high risk pipeline sections and sites are predictable. Sensors can be embedded at these strategic sites to collect data that contain ‘predictor features’ signifying the occurrence of localised corrosion, CP failure, coating disbondment and degradation. Information from these sensors will enable pipeline owners to prioritise site survey and inspection operations, and to develop maintenance strategy to manage aged pipelines, rather than replace them.

Reutilização de imóveis de interesse patrimonial, voltados para a ahabitação: um estudo de caso na Ribeira-Natal/RN

This work analyzes the reutilization of real estate of patrimonial interest, come back toward habitation. One understands as real estate of patrimonial interest the old ones that present relevant architectural typologies that must be preserved; some buildings that represent characteristic architectural styles of a determined period; some valued real estates for the history of the city (historical, memory and image signification that has of certain places) and buildings with exceptional artistic elements. In short, real estate of patrimonial interest. The place or site to be studied will be the neighborhood of the Ribeira, because is an area that protects a bigger interest for the historic patrimony of the city. The habitation use was thought as a booster element of revitalization processes of degradable historic site, contributing to the preservation of artistic, architectural and historic patrimony, and thus to stimulate the accomplishment of the re-qualification of the neighborhood of the Ribeira. It is intended with the present study to examine alternatives to make possible habitation re (uses) in the historical quarter of the Ribeira in old constructions of patrimonial value

The structure of a native L-amino acid oxidase, the major component of the Vipera ammodytes ammodytes venomic, reveals dynamic active site and quaternary structure stabilization by divalent ions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Characterization of humic-rich hydrocolloids and their metal species by means of competing ligand and metal exchange - an on-site approach

An improved on-site characterization of humic-rich hydrocolloids and their metal species in aquatic environments was the goal of the present approach. Both ligand exchange with extreme chelators ( diethylenetetraaminepentaacetic acid ( DTPA), ethylendiaminetetraacetic acid ( EDTA)) and metal exchange with strongly competitive cations (Cu(II)) were used on-site to characterize the conditional stability and availability of colloidal metal species in a humic-rich German bogwater lake ( Venner Moor, Munsterland). A mobile time-controlled tangential-flow ultrafiltration technique (cut-off: 1 kDa) was applied to differentiate operationally between colloidal metal species and free metal ions, respectively. DOC ( dissolved organic carbon) and metal determinations were carried out off-site using a home-built carbon analyzer and conventional ICP-OES ( inductively-coupled plasma-optical emission spectrometry), respectively. From the metal exchange equilibria obtained on-site the kinetic and thermodynamic stability of the original metal species ( Fe, Mn, Zn) could be characterized. Conditional exchange constants K ex obtained from aquatic metal species and competitive Cu(II) ions follow the order Mn > Zn >> Fe. Obviously, Mn and Zn bound to humic-rich hydrocolloids are very strongly competed by Cu( II) ions, in contrast to Fe which is scarcely exchangeable. The exchange of aquatic metal species (e.g. Fe) by DTPA/EDTA exhibited relatively slow kinetics but rather high metal availabilities, in contrast to their Cu(II) exchange.

Diagnostic de securite d'une entreprise bresilienne a partir de l'analyse des accidents du travail par la methode de l'arbre des causes

We present here the results of a study of 21 work-related accidents that occurred in a Brazilian manufacturing company. The aim was to assess the safety level of the company to improve its work accident prevention policy. In the last 6 months of 1992 and 1993, all accidents resulting in 15 days' absence from work, reported for social security purposes, were analyzed using the INRS causal tree method (ADC) and a questionnaire completed on site. Potential risk factors for accidents were identified based on the specific factors highlighted by the ADC. More universal trees were also compiled for the safety assessment. Three hundred and thirty specific accident factors were recorded (man of 15.71 per accident). This is consistent with there being multiple causes of accidents rather than the assertion of Brazilian business safety departments that accidents are due to 'dangerous' or 'unsafe' behavior. Introducing the idea of culpability into accidents prevents the implementation of an appropriate information feedback process, essential for effective prevention. However, the large number of accidents related to 'material' (78%) and 'environment' (70%) indicates that working conditions are poor. This shows that the technical risks, mostly due to unsafe machinery and equipment are not being dealt with. Seventy-five potential accident factors were identified. Of these, 35% were 'organizational', a high proportion for the company studied. Improvisation occurs at all levels, particularly at the organizational level. This is, thus a major determinant for entire series of, if not most, accident situations. The poor condition of equipment also plays a major role in accidents. The effects of poor equipment on safety exacerbate the organizational shortcomings. The company's safety intervention policy should improve the management of human resources (rules designating particular workers for particular workstations; instructions for the safe operation of machines and equipment; training of operators, etc.) and introduce programs to detect risks and to improve the safety of machines and equipment. We also recommend the establishment of a program to follow the results of any preventive measures adopted.