Journal articles on the topic 'Curatorial and Related Studies not elsewhere classified'

Purpose The purpose of this paper is to investigate the main causes of delay in public construction projects. This is motivated by feedback from public construction experts concerning substantive delays during the last decade. The study thus seeks to help decision makers in Jordan and elsewhere identify problems and develop mitigating strategies. Design/methodology/approach Causes of delay were identified from previous related studies and then augmented after consultation with experts. This resulted in 56 delay factors classified into eight groups. The sampling frame for the study was defined in terms of public construction projects (mostly related to roads) owned by the Ministry of Public Works and Housing in Jordan. A survey was conducted with engineers working as representatives of the owner, contractors or consultants to elicit and evaluate the importance of the 56 delay factors. Findings Overall, 113 completed questionnaire responses were returned and analyzed to rank the causes of delay using the relative importance index method. Owners and consultants showed more interest in factors related to themselves, while contractors showed highest interest in an external factor related to the owner of services. Four recommendations are put forward for decision makers to mitigate against delays. Originality/value This research investigates a relatively large number of delay factors compared to other studies and these are categorized into groups to facilitate thematic understanding. Further, compared to previous related research, this research fills a gap by exploring the opinions of different contract parties.

Objectives: To review the literature evaluating outcomes resulting from expansion of the bipolar disorder (BD) diagnostic category. We were particularly interested in identifying high-level evidence for improved clinical outcomes as documented by randomized controlled trials (RCTs) or cohort studies. Methods: The English-language literature was searched using Ovid MEDLINE for studies of BD referenced against the key word spectrum. We used bibliographies and other databases to extend this search when no relevant RCTs or relevant cohort studies were identified. Results: In the MEDLINE searches, abstracts and titles of 86 studies were examined and 48 were found to be related to the topic of bipolar spectrum disorders (BSD). No RCTs or prospective cohort studies evaluating modified diagnostic or therapeutic practices were identified. The literature about the BSD consists mostly of expert opinion emphasizing: various links between bipolar and unipolar mood disorders; a proposal that a greater proportion of the population without a mood disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders should be diagnosed under the BD category; and, proposals that syndromes currently classified elsewhere should be subsumed under the BD category. Conclusions: Our search failed to uncover high-level evidence demonstrating the clinical utility of proposed diagnostic realignments. The widespread acceptance of the expanded spectrum concept appears to be based on interpretation of descriptive epidemiologic data by high-profile experts.

Abstract. Studies of secondary aerosol-particle formation depend on identifying days in which new particle formation occurs and, by comparing them to days with no signs of particle formation, identifying the conditions favourable for formation. Continuous aerosol size distribution data has been collected at the SMEAR II station in a boreal forest in Hyytiälä, Finland, since 1996, making it the longest time series of aerosol size distributions available worldwide. In previous studies, the data have been classified as particle-formation event, nonevent, and undefined days, with almost 40% of the dataset classified as undefined. In the present study, eleven years (1996–2006) of undefined days (1628 days) were reanalyzed and subdivided into three new classes: failed events (37% of all previously undefined days), ultrafine-mode concentration peaks (34%), and pollution-related concentration peaks (19%). Unclassified days (10%) comprised the rest of the previously undefined days. The failed events were further subdivided into tail events (21%), where a tail of a formation event presumed to be advected to Hyytiälä from elsewhere, and quasi events (16%) where new particles appeared at sizes 3–10 nm, but showed unclear growth, the mode persisted for less than an hour, or both. The ultrafine concentration peaks days were further subdivided into nucleation-mode peaks (24%) and Aitken-mode peaks (10%), depending on the size range where the particles occurred. The mean annual distribution of the failed events has a maximum during summer, whereas the two peak classes have maxima during winter. The summer minimum previously found in the seasonal distribution of event days partially offsets a summer maximum in failed-event days. Daily-mean relative humidity and condensation sink values are useful in discriminating the new classes from each other. Specifically, event days had low values of relative humidity and condensation sink relative to nonevent days. Failed-event days possessed intermediate condensation sink and relative humidity values, whereas both ultrafine-mode peaks and, to a greater extent, pollution-related peaks had high values of both, similar to nonevent days. Using 96-h back trajectories, particle-size concentrations were plotted as a function of time the trajectory spent over land. Increases in particle size and number concentration during failed-event days were similar to that during the later stages of event days, whereas the particle size and number concentration for both nonevent and peaks classes did not increase as fast as for event and failed events days.

Abstract. Studies of secondary aerosol-particle formation depend on identifying days in which new particle formation occurs and, by comparing them to days with no signs of particle formation, identifying the conditions favourable for formation. Continuous aerosol size distribution data has been collected at the SMEAR II station in a boreal forest in Hyytiälä, Finland, since 1996, making it the longest time series of aerosol size distributions available worldwide. In previous studies, the data have been classified as particle-formation event, nonevent, and undefined days, with almost 40% of the dataset classified as undefined. In the present study, eleven years (1996–2006) of undefined days (1630 days) were reanalyzed and subdivided into three new classes: failed events (37% of all previously undefined days), ultrafine-mode concentration peaks (34%), and pollution-related concentration peaks (19%). Unclassified days (10%) comprised the rest of the previously undefined days. The failed events were further subdivided into tail events (21%), where a tail of a formation event presumed to be advected to Hyytiälä from elsewhere, and quasi events (16%) where new particles appeared at sizes 3–10 nm, but showed unclear growth, the mode persisted for less than an hour, or both. The ultrafine concentration peaks days were further subdivided into nucleation-mode peaks (24%) and Aitken-mode peaks (10%), depending on the size range where the particles occurred. The mean annual distribution of the failed events has a maximum during summer, whereas the two peak classes have maxima during winter. The summer minimum previously found in the seasonal distribution of event days partially offsets a summer maximum in failed-event days. Daily-mean relative humidity and condensation sink values are useful in discriminating the new classes from each other. Specifically, event days had low values of relative humidity and condensation sink relative to nonevent days. Failed-event days possessed intermediate condensation sink and relative humidity values, whereas both ultrafine-mode peaks and, to a greater extent, pollution-related peaks had high values of both, similar to nonevent days. Using 96-h back trajectories, particle-size concentrations were plotted as a function of time the trajectory spent over land. Increases in particle size and number concentration during failed-event days were similar to that during the later stages of event days, whereas the particle size and number concentration for both nonevent and peaks classes did not increase as fast as for event and failed events days.

Viruses that are normally safely contained within their host spe­cies can emerge due to intense livestock farming, trade, travel, climate change and encroachment of human activities into new environments. The unexpected emergence of bluetongue virus (BTV), the prototype species of the genus Orbivirus, in economi­cally important livestock species (sheep and cattle) across the whole of Europe (since 1998), indicates that other orbiviruses represent a potential further threat to animal and human popula­tions in Europe and elsewhere. The genus Orbivirus is the largest within the family Reoviridae, containing 22 virus species, as well as 14 unclassified orbiviruses, some of which may repre­sent additional or novel species. The orbiviruses are transmitted primarily by arthropod vectors (e.g. Culicoides, mosquitoes or ticks). Viral genome sequence data provide a basis for virus taxonomy and diagnostic test development, and make it possible to address fundamental questions concerning virus biology, pathogenesis, virulence and evolution, that can be further explored in mutation and reverse genetics studies. Genome sequences also provide criteria for the classification of novel isolates within individual Orbivirus species, as well as the identification of different sero­types, topotypes, reassortants and even closely related but dis­tinct virus lineages. Full-length genome characterization of Tilligerry virus (TILV), a member of the Eubenangee virus species, and Mitchell River virus (MRV), a member of the Warrego virus species, have revealed highly conserved 5’ and 3’ terminal hexanucleotide sequences. Phylogenetic analyses of orbivirus T2 ‘sub-core-shell’ protein sequences reinforce the hypothesis that this protein is an important evolutionary marker for these viruses. The T2 protein shows high levels of amino acid (AA) sequence identity (> 91%) within a single Orbivirus species / serogroup, which can be used for species identification. The T2-protein gene has therefore been given priority in sequencing studies. The T2 protein of TILV is closely related to that of Eubenangee virus (~91% identity), con­firming that they are both members of the same Eubenangee virus species. Although TILV is reported to be related to BTV in serological assays, the TILV T2 protein shows only 68-70% AA identity to BTV. This supports its current classification within a different serogroup (Eubenangee). Warrego virus and MRV are currently classified as two distinct members (different serotypes) within the Warrego virus species. However, they show only about 79% AA identity in their T2 pro­tein (based on partial sequences). It is therefore considered likely that they could be reclassified as members of distinct Orbivirus species. The taxonomic classification of MRV will be reviewed after generating full length sequences for the entire genomes of both viruses. The taxonomic status of each of these viruses will also be tested further by co-infections and attempts to create reassortants between them (only viruses belonging to the same species can reassort their genome segments). TILV and MRV are the first viruses from their respective serogroups / virus species to be genetically fully characterized, and will provide a basis for the further characterization / identification of additional viruses within each group / species. These data will assist in the devel­opment of specific diagnostic assays and potentially in control of emerging diseases. The sequences generated will also help to evaluate current diagnostic [reverse transcriptase - polymerase chain reaction (RT-PCR)] tests for BTV, African horse sickness virus, epizootic haemorrhagic disease virus, etc., in silico, by identifying any possibility of cross reactivity.

Abstract Efficacy, safety, together with molecular and immunological biomarkers were studied in a sequential clinical trial of neoadjuvant immunotherapy, surgery and adjuvant immunotherapy in locally advanced or oligometastatic melanoma patients (pts), within an open label, single arm and two sites study. Treatment schedule consisted in four primary cycles of inverted dose ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks, followed by radical surgery and adjuvant nivolumab 480 mg every 4 weeks for 6 cycles. Primary objective was pathological complete remission (pCR) rate, according to International Neoadjuvant Melanoma Consortium (INMC) criteria, while secondary objectives were: safety, feasibility and efficacy; QoL; identification of biomarkers of response and resistance; degree of immune activation; longitudinal evaluation of the gut microbiome. From March 2019 to April 2021, 43 pts were enrolled in the trial and, with an intent to treat of 35 pts, 34 completed the primary phase, 31 received surgery and 28 completed the adjuvant phase. Four pts were withdrawn during primary phase for progression (2), toxicity (1) and consent withdrawal (1). Study primary endpoint has been met since 20/31 pts undergoing surgery reached a pCR/near pCR (65%), 4/31 (13%) a pathological partial remission (pPR) and 7/31 (22%) pts a pathological no response. With a median follow-up of 17 months, 33/35 pts are alive. Treatment failure occurred in 9 pts: 2 pts progressed during primary phase and did not undergo surgery; 7 pts progressed during adjuvant (3 pts) or follow-up phase (4 pts). Six out of these 7 pts were classified as pNR at surgery, while the other, classified as pCR, did not receive adjuvant therapy. Both pts in stage IV relapsed. Unfortunately, one pt died for ischemic stroke after 5 months from adjuvant therapy while on CR. Treatment related toxicities were mainly G1-2 and only 6 pts (17%) developed G3-4 adverse events (AE): 3 transaminitis, 1 pneumonitis, 1 myocarditis, 1 CPK increase and 1 dermatomyositis. Translational studies on samples collected before, during therapy and at progression have been performed: whole exome sequencing and gut microbiota dynamics on longitudinal samples showed some relationships with responses and developing resistances. These data, never presented elsewhere previously, are in part new and in part confirmatory of immunological or molecular signatures described by other groups. In conclusion, primary immunotherapy with Ipilimumab/Nivolumab in pts affected by locally advanced/oligometastatic melanoma is able to achieve an elevated pCR/near pCR rate which appears to be predictive of long term relapse free survival. Translational data analyzed longitudinally on each patient can allow for a better selection of pts, giving new insight on the mechanisms of melanoma progression and resistance. Citation Format: Pier Francesco Ferrucci, Bruno Achutti Duso, Luigi Nezi, Luca Mazzarella, Fiorenza Lotti, Sara Gandini, Gianmarco Orsolini, Elisabetta Pennacchioli, Patrizia Gnagnarella, Teresa Manzo, Simone Ribero, Maria Teresa Fierro, Rebecca Senetta, Concetta Riviello, Virginia Caliendo, Pietro Quaglino, Massino Barberis, Giuseppina Bonizzi, Emilia Cocorocchio. Neoadjuvant ipilimumab/nivolumab in locally advanced or oligometastatic melanoma: An open label, single arm, multi-institutional clinical study with molecular and immunological biomarker’s analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT167.

The paper deals with the effects of prescriptivism on the Lithuanian language. The research includes one domain of language use – radio and television, and one aspect of language – lexicon, in the period between 1960 and 2010. The investigation is corpus-based and focuses on the use of words that are classified as “incorrect” by the Lithuanian norm-setters. The study is important both as a discussion of the impact of prescriptivism on language change in general, as well as of the indirect influence of media on language, since media can affect the symbolic evaluation of specific language forms.The paper consists of five chapters. The first chapter “Review of the research” discusses the theoretical assumptions and concepts needed for further analysis: it gives an overview of studies on the effects of prescriptivism conducted in Lithuania and elsewhere, presents the concepts of second-level indexicality and style, and outlines the key characteristics of media change in Lithuania that are relevant to the study. Studies on the success of prescriptivism do not give a definite answer as to whether prescriptivism works. Institutionalisation and a high degree of stigmatisation of the corrected language forms can be listed among the factors that increase its success; prescriptivism is likely to be less successful when the “forbidden” language forms are too convenient to be given up, or when prescriptivist rules are too complicated for lay language users and the rules contradict each other. In the case of media, the effect of prescriptivism is said to be weakened by media commercialisation.When applied to the analysis of non-standard words, first-order indexicality refers to situations when the non-standard forms are used as value-free instances of ordinary speech, in already established meanings; in these cases, the speakers are not aware that they are using “incorrect” forms. Second-order indexicality refers to cases when non-standard words are used for additional function, e.g., to express a speaker’s particular identity or to construct a certain (informal, friendly) speech style. The concept of style, referring to the social differences between individual speakers, is used to analyse the use of words in concrete situations. The paper gives an overview of three sociolinguistic concepts of style that are relevant in this study: style as a degree of formality (e.g., when the speaker accommodates to the formal context of the media and uses less non-standard words); as audience and referee design (e.g., use of non-standard words in programmes for young audiences); and as a speaker design (e.g., play with language by the programme host in order to construct a fun persona).In the study of non-standard lexis, it is important to account for certain features of Lithuanian media development, such as the Soviet period, which was characterised by the use of newspeak, and the commercialisation of the media in the contemporary period. Accordingly, the paper analyses the uses of incorrect words as a part of newspeak and their use for the entertainment-related purposes such as language plays in present times. The paper also addresses the transitory period of radio and TV development, which has features from both the previous and the later periods, as well as some unique characteristics of language use.The second chapter “Radio and TV speech in the prescriptive discourse” presents an analysis of the metalinguistic discourse on media speech produced by Lithuanian prescriptivists from the pre-war period up to now. The analysis shows how this discourse preserved the same dominant idea about media’s role in language standardisation. On the one hand, during this whole time, radio and television were approached as responsible for teaching listeners and viewers the “correct language”; on the other hand, simultaneously, the language of radio and television was perceived as failing to conform to the prescriptive norms set by the norm-setters. The huge societal shifts that happened during this time did not make a major influence on this discourse. It remained very stable during different periods of time. The social, cultural and political changes in society and the media were taken into account only by adjusting the argumentation – by presenting patriotic, moral, ideological or legal motives that were meant to justify the language prescriptions.The third chapter “Research methods and data” presents the Corpus of Radio and TV speech, the concept of non-standard words, and the sources of prescriptivist corrections used in the analysis. The corpus of radio and TV speech includes data from 1960 to 2011 and is constructed in a balanced way to represent the periods of Lithuanian radio and TV development (Soviet, transitory, contemporary), as well as programme genres (talk programmes, information programmes, journals/features/documentaries). The speakers are coded into six types: news reader/voice-over, talk show host, expert, celebrity, hero and vox populi. For the analysis, the non-standard words that are classified as “incorrect” in the normative tradition of the Lithuanian language were coded. These include old (mainly, Slavic) and new (mainly, English) loans, the so-called hybrid words (that have a borrowed part), semantic loans, translations, as well as some lexicalised uses of words and some lexicalised syntactic constructions. Two types of words are analysed – individual lexical words and functional words. The latter include various fillers and discourse markers, as well as pronoun constructions with tai (e.g. kažkas tai ‘some(body)’). Non-standard words were identified from older and present style guides, including the database of language corrections created by the State Commission of the Lithuanian Language.The fourth chapter “Change in the number of non-standard words: a quantitative analysis” investigates development of the use of non-standard words on radio and TV, as well as the frequency of usage of the non-standard lexical forms. According to the corpus data, the average frequency of non-standard words by one speaker is 17 per thousand words, which makes up about 2–3 “incorrect” words per minute. Non-standard discourse markers and fillers (9.8/1000 words) are used most frequently, whereas individual lexical words (5.6/1000 words) are much less frequent, and pronoun constructions with tai (1.6/1000 words) are rarer still. Closer analysis revealed that the only statistically significant change between the analysed periods (Soviet, transitory and contemporary) was a decrease of the frequency of non-standard lexical words in the contemporary period compared to the previous ones. The frequency of discourse markers/fillers and pronoun constructions with tai did not change. Regarding the speaker types, the uses of non-standard words decreased in those groups that are within easier reach of prescriptivism – news readers/voice-overs and talk show hosts. Also, to a lesser extent, in the group of experts. Those groups of speakers that are less likely to be subjected to language correction practices (ordinary people) did not seem to change their behaviour: the number of non-standard words in their speech did not decrease, on the contrary, a slight increase has been noticed. These findings confirm the effects of institutionalised prescriptivism. Regarding genres, non-standard words are least frequent in information programmes, which are mostly based on the reading of written texts. Lists of the most frequent non-standard words during the three periods overlap to a great extent, which means that despite prescriptivist practices, the most frequent non-standard words do not disappear from the air.The fifth chapter “Change in the functions of non-standard words: a qualitative analysis” investigates specific communicative situations of the usage of non-standard words and takes into account the media-related and societal contexts, as well as the stylistic and social functions of the corrected lexis. A common trait of the use of non-standard words during all periods, interpreted as the first level of indexicality, is the use of common, everyday vocabulary, most likely without being aware of the “incorrect” status of the chosen forms. Also, non-standard words are used as a part of professional language, in this case the speaker might be aware that he or she is using an ‘incorrect’ word, but chooses to use it nevertheless for convenience or because of its indexical value for professional identity. During all the periods, non-standard words are also used as indices of informal and authentic communication between close acquaintances; this function is performed by all types of the studied non-standard words, particularly old borrowings and frequent fillers.The study identified a few style- and social meaning-related uses of non-standard lexis that explain the choice of the corrected forms instead of the required equivalents. In the Soviet period, some non-standard words were used as a part of Soviet newspeak; old borrowings were used in references to the ideological enemies of Soviet rule, mainly the ones from pre-war Lithuania. In certain cases, these words were employed due to their stylistic value in an intimate and authentic discourse. The late Soviet period saw the first use of non-standard words as markers of informal communication. The use of non-standard words in the transitory period shows some of the functions from the Soviet period, e.g., they are used as an element of newspeak, albeit without the Soviet ideological value, or as expressions of informality. A particular feature of this period is the use of non-standard words as an index of live and authentic speech, which was not allowed during Soviet times, as a means of authentic communication, and the criticism and violation of Soviet taboos. The contemporary period is marked by a huge variety of functions of non-standard words. It brings in a number of new style-related functions of non-standard words: construction of youth-oriented identity and youth-oriented referee design, reference to past times (e.g., by using non-standard words reflecting the Soviet reality), or quoting. Perhaps the most distinctive features of this period are the use of non-standard words in the speech of professional journalists, as well as their use for the purposes of humour and entertainment (for the construction of certain personas), e.g., in language plays and stylisations. These uses can be explained by commercial media requirements, increasing trends of the informalisation of public speech and conversationalisation.The study concluded that the effect of prescriptivism on the use of non-standard words in radio and TV in Lithuania is limited. Firstly, the frequency of non-standard words decreased mainly in those groups of speakers that are subject to the formal, institutionalised power of language gatekeepers (media professionals). Secondly, the data shows a decrease only of those non-standard words that are easier to control by the speakers themselves – lexical words. The frequency of various function words that are more difficult to be aware of when speaking did not decrease. Thirdly, the largest decrease in non-standard lexical forms occurred in those speech situations where a prepared written text is used; this means that prescriptivist requirements have a greater effect when the speakers and the language are controlled, and less effect in spontaneous communication situations. The above-mentioned difference between professional and non-professional speakers demonstrates that speakers are able to control the lexical forms they choose.Analysis of the most frequently used non-standard words during different periods also demonstrates the limits of prescriptivism. The lists of the most frequently used non-standard words during different periods overlap to a great extent, which means that despite prescriptivist efforts, they were not eliminated from being used on air.Finally, the limited success of prescriptivism is demonstrated by the discussed social values of non-standard words, when they are used for various social and stylistic functions not possessed by a ‘correct’ equivalent. The qualitative analysis revealed the particular strength of old borrowings, which are used to create a sincere, friendly speech style, as well as a ludic speaker identity. On the one hand, it can be interpreted as a sign of the ineffectiveness of prescriptivism – if the words are needed, it is likely that they will be further used despite their ‘illegal’ status. On the other hand, when the speakers purposefully (e.g., on account of a particular association, stylistic value) choose a particular language form and are at the same time aware about its “incorrectness”, it is an effect of prescriptivism, only with the opposite outcome.The study is based on the analysis of spoken language on radio and TV, therefore it cannot be used to draw conclusions about the Lithuanian language in general. It is likely that the effect of prescriptivism on written language (because of its more formal style and particularly because of language editing practices) would be stronger. Nevertheless, broadcast media speech constitutes a considerable and important part of language use, thus we can conclude that the impact of prescriptivism on the Lithuanian language does not have far-reaching effects.

Helicobacter pylori is the leading cause of peptic ulcer disease. The infection has been implicated in more than 75% of duodenal ulcer cases and 17% of gastric ulcer cases. H. pylori has been classified as a human carcinogen, since it is the main cause of distal gastric adenocarcinoma and B cell mucosa-associated lymphoid tissue lymphoma. Evidence also links H. pylori with extragastric conditions including iron deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency. Studies indicate that H. pylori may be protective against other conditions of the gastrointestinal tract (e.g., reflux esophagitis and related pathologies) and elsewhere in the body (e.g., asthma). The infection is asymptomatic in the vast majority of cases; more serious outcomes occur in only 10–15% of infected individuals. Despite extensive research over the past 3 decades, there is no effective vaccine, and the circumstances leading to disease development remain unclear. In addition, there is now a growing prevalence of antimicrobial resistance in H. pylori. This review discusses these important issues. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Abstract Case report - Introduction Scleritis is severe vision-threatening scleral inflammation, commonly presenting with a red, painful eye and can be classified using the Watson system. Posterior scleritis may present with associated anterior uveitis in many cases. Steroid therapy is often successful initially; however, further immunomodulation is usually required to control subsequent episodes which can be challenging. We present an 18-year-old, Caucasian girl with a left eye, sight-threatening, steroid-dependent posterior uveitis who required escalation of treatment to tocilizumab before inflammation could be suppressed. Case report - Case description Our patient was diagnosed elsewhere with ulcerative colitis at the age of 12 and subsequently developed recurrent episodes of uveitis and scleritis which could be controlled with topical steroids. At the age of 16 she presented with an inflammatory arthritis and was treated with intravenous methylprednisolone before commencing sulfasalazine therapy. Due to persistent systemic and ophthalmic inflammation she was changed to adalimumab; however, this was also unsuccessful and methotrexate was added. By the age of 18 she had been steroid-dependent for 2 years and could not reduce daily prednisolone below 15mg without a deterioration in her left eye posterior scleritis with visual acuity compromise including episodes of complete visual loss causing high levels of anxiety. Due to the pain and deterioration in vision she struggled with her studies and school attendance, and withdrew from her passion for competitive sailing. With ongoing sight-threatening inflammatory changes she was referred for further tertiary assessment in 2019. During the following 4 months treatment was escalated rapidly. Methotrexate dose was increased, and adalimumab frequency reduced to weekly. There was a limited response, with further episodes of sight deterioration as a result of flares in inflammation. Response to tocilizumab treatment was seen after only two doses with good control of scleritis by 3 months of treatment when steroids were successfully weaned and stopped. Over 18 months of tocilizumab therapy the patient has only required one course of topical steroids for mild ocular inflammation which resolved without any other treatment required. She has successfully completed her degree, can complete daily gym training sessions and participate in regular sailing competitions. Case report - Discussion Posterior scleritis is the most common scleritis in children and can be associated with anterior uveitis, concurrent anterior scleritis, disc swelling or retinal striae. Posterior scleritis has a higher rate of complications therefore is treated aggressively. Refractory cases such as this require biologic therapy and rituximab is often used. Despite the preference of two adult eye units for treatment with rituximab the rationale for tocilizumab included; recent high quality studies showing successful treatment of inflammatory bowel disease, its known benefit for anterior uveitis and case studies in adults with posterior scleritis. Tocilizumab is a recombinant monoclonal antibody that causes a blockade of interleukin-6 receptors. It is currently only approved by the Food and Drug Administration (FDA) for use in children with polyarticular or systemic onset Juvenile Idiopathic Arthritis (JIA). Our patient had a very positive experience with this drug, no side effects and rapid clinical improvement seen. As a result her quality of life and mental health improved quickly. Case report - Key learning points This is a case of refractory, sight-threatening, steroid-dependent posterior scleritis on a background of inflammatory bowel disease and arthritis. As a result of this case our team reviewed current literature from other paediatric populations and adults with scleritis, informing the clinical decision to proceed with tocilizumab after control was unsuccessful with previous agents. The remarkable response demonstrated for our patient highlights the value tocilizumab can offer to the treatment options for similar refractory cases. This adds to the growing positive data published surrounding tocilizumab in children but further studies in paediatric populations are required to evaluate this in greater detail.

Abstract Background Patients calling for an emergency ambulance and assessed as presenting with ‘unclear problem’ account for a considerable part of all emergency calls. Previous studies have demonstrated that these patients are at increased risk for unfavourable outcomes. A deeper insight into the underlying diagnoses and outcomes is essential to improve prehospital treatment. We aimed to investigate which of these diagnoses contributed most to the total burden of diseases in terms of numbers of deaths together with 1- and 30-day mortality. Methods A historic regional population-based observational cohort study from the years 2016 to 2018. Diagnoses were classified according to the World Health Organisation ICD-10 System (International Statistical Classification of Diseases and Related Health Problems, 10th edition). The ICD-10 chapters, R (‘symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified)’ and Z (‘factors influencing health status and contact with health services”) were combined and designated “non-specific diagnoses”. Poisson regression with robust variance estimation was used to estimate proportions of mortality in percentages with 95% confidence intervals, crude and adjusted for age, sex and comorbidities. Results Diagnoses were widespread among the ICD-10 chapters, and the most were ‘non-specific diagnoses’ (40.4%), ‘circulatory diseases’ (9.6%), ‘injuries and poisonings’ (9.4%) and ‘respiratory diseases’ (6.9%). The diagnoses contributing most to the total burden of deaths (n = 554) within 30 days were ‘circulatory diseases’ (n = 148, 26%) followed by ‘non-specific diagnoses’ (n = 88, 16%) ‘respiratory diseases’ (n = 85, 15%), ‘infections’ (n = 54, 10%) and ‘digestive disease’ (n = 39, 7%). Overall mortality was 2.3% (1-day) and 7.1% (30-days). The risk of mortality was highly associated with age. Conclusion This study found that almost half of the patients brought to the hospital after calling 112 with an ‘unclear problem’ were discharged with a ‘non-specific diagnosis’ which might seem trivial but should be explored more as these contributed the second-highest to the total number of deaths after 30 days only exceeded by ‘circulatory diseases’.

Abstract Objective To determine publication trends, gaps, and predictors of citation of chiropractic case reports (CRs). Methods A bibliometric review was conducted by searching PubMed, Index to Chiropractic Literature (ICL), and Google Scholar to identify PubMed-indexed CRs, which were screened according to selection criteria. Case reports were categorized by International Classification of Disease (ICD-10) code, patient age, topic describing case management or adverse effects of care, focus being spinal or non-spinal, journal type, integrative authorship, title metrics, and citation metrics. Binary logistic regression was used to identify independent predictors of citations per year and total citations greater than the median values. Results The search identified 1176 chiropractic CRs meeting selection criteria. There was an increasing trend of CRs having a case management topic, non-spinal focus, non-chiropractic journal, neuromusculoskeletal-focus, diagnosis of vascular pathology, and a decreasing trend of adverse effect vascular pathology CRs. Independent predictors of greater total citations (or citation rate) included ICD-10 categories of perinatal conditions, infections, “case” in title, case management topic, and physical therapy, integrative, and dental journal type. Predictors of fewer citations included diseases of the blood, neoplasms, other findings not elsewhere classified, a title > 11 words, and multidisciplinary authorship. ICD-10 categories describing non-musculoskeletal diseases and special populations such as pediatrics, pregnancy, and perinatal conditions had few CRs. Conclusion Chiropractic CRs are diversifying from spine-related topics. Chiropractors are encouraged to publish objective, structured CRs within defined research gaps. Published CRs can inform the design of future research studies with a higher level of clinical relevance and evidence.

Introduction: Early readmission after PCI can be a useful performance measure, particularly if the reasons for readmission are related to patient management (e.g. angina, stent thrombosis or bleeding). Prior studies on readmission have used principal billing discharge diagnosis, but the validity of billing codes for this purpose is unclear. Methods: PCI patients readmitted within 30 days of discharge at the Massachusetts General Hospital (January 2007-December 2011) and Brigham and Women’s Hospital (June 2009-December 2011), were identified, and their medical records reviewed by a cardiologist. For each readmission, the principal billing discharge diagnosis of the readmission was compared to the primary diagnosis of the readmission as determined by the chart review. The accuracy of billing discharge diagnoses for readmissions due to chest pain or other symptoms concerning for angina and vascular access complications was assessed. Results: Of 9081 patients undergoing PCI and surviving to hospital discharge, 1011 (11.1%) were readmitted to the index hospital within 30 days. After excluding repeat readmissions, 894 readmissions were reviewed and of those, 754 (84.3%) could be matched to billing diagnoses. For each reason for readmission, corresponding billing diagnoses were diverse (Table 1). The sensitivity and specificity of billing code 414.01 for a readmission for chest pain or other symptoms concerning for angina were 0.36 and 0.85, respectively. The sensitivity and specificity of billing code 997.2 (Peripheral vascular complications, not elsewhere classified) for a bleeding or vascular complication of PCI were 0.28 and 0.997, respectively. Conclusions: The diversity of ICD-9 codes does not allow straightforward categorization of principal diagnoses of readmission from billing data. More complex algorithms need to be developed and validated to reliably derive reasons for readmission after PCI from billing data.

There’s always this never-ending discussion about the curator who imposes meaning or imposes the concept of art, of what art is. I think this is the wrong opposition. Every artwork produces its concept, or a concept of what art is. And the role of the curator is not to produce a concept of art but to invent, to fabricate, elaborate reading grids or coexistence grids between them.(Nicolas Bourriaud quoted in Bourriaud, Lunghi, O’Neill, and Ruf 91–92)In 2010 at a conference in Rotterdam, Nicolas Bourriaud, Enrico Lunghi, Paul O’Neill, and Beatrix Ruf discussed the question, “Is the curator per definition a political animal?” This paper draws on their discussion when posing the reverse scenario—is the political animal per definition a curator in the context of the development of large-scale public policy? In exploring this question, I suggest that recent conceptual discussions centring on “the curatorial turn” in the arena of the creative arts provide a useful framework for understanding and managing opportunities and pitfalls in policymaking that is influenced by news media. Such a conceptual understanding is important. My empirical research has identified a transport policy arena that is changing due to news media scrutiny in Sydney, Australia. My findings are that the discourses arising and circulating in the public and the news media wield considerable influence. I posit in this paper the view that recent academic discussion of curatorial practices could identify more effective and successful approaches to policy development and implementation. I also question whether some of the key problems highlighted by commentary on the curatorial turn, such as the silencing of the voice of the artist, find parallels in policy as the influence of the bureaucrat or technical expert is diminished by the rise of the politician as curator in mediatised policy. The Political AnimalPaul O’Neill defines a political animal: “to be a passionate and human visionary—someone who bridges gaps, negotiates the impossible in order to generate change, even slight change, movements, a shivering” (Bourriaud et al. 90). O’Neill’s definition is a different definition from Aristotle’s famous assertion that humans (collectively) are the “political animal” because they are the only animals to possess speech (Danta and Vardoulakis 3). The essence of O’Neill’s definition shifts from the Aristotelian view that all humans are political, towards what Chris Danta and Dimitris Vardoulakis (4) refer to as “the consumption of the political by politics,” where the domain of the political is the realm of the elite few rather than innately human as Aristotle suggests. Moreover, there is a suggestion in O’Neill’s definition that the “political animal” is the consummate politician, creating change against great opposition. I suggest that this idea of struggle and adversity in O’Neill’s definition echoes policy development’s own “turn” of the early 1990s, “the argumentative turn in policy analysis and planning” (Fischer and Forester 43). The Argumentative Turn The argumentative turn in policy analysis and planning is premised on the assertion that “policy is made of language” (Majone 1). It represents a seismic shift in previously championed academic conceptions of policy analysis—decisionism, rationality, the economic model of choice, and other models that advocate measured, rational, and objective policy development processes. The argumentative turn highlights the importance of communication in policy development. Prior to this turn, policy analysts considered formal communication to be something that happened after policy elites had completed the scientific, objective, analytical, and rational work. Communication was perceived as being the process of “seducing” or the “‘mere words’ that add gloss to the important stuff” (Throgmorton 117–19). Communication had meant selling or “spinning” the policy—a task often left to the devices of the public relations industry by the “less scrupulous” policymaker (Dryzek 227).The new line of inquiry posits the alternative view that, far from communication being peripheral, “the policy process is constituted by and mediated through communicative practices” (Fischer and Gottweis 2). Thanks largely to the work of Deborah Stone and Giandomenico Majone, academics began to ask, “What if our language does not simply mirror or picture the world but instead profoundly shapes our view of it in the first place?” (Fischer and Forester 1). The importance of this turn to the argument, I posit in this paper, is illustrated by Stone when she contends that the communication of conflicting views and interests create a world where paradoxical positions on policy are inevitable. Stone states, “Ask a politician to define a problem and he will probably draw a battlefield and tell you who stands on which side. The analytical language of politics includes ‘for and against,’ ‘supporters and enemies,’ ‘our side and their side’” (166). Stone describes a policymaking process that is inherently difficult. Her ideas echo O’Neill’s intonation that in order for movement or even infinitesimal change it is the negotiation of the impossible that makes a political animal. The Mediatisation of Sydney Transport Stone and Majone speak only cursorily of the media in policy development. However, in recent years academics have increasingly contended that “mediatisation” be recognised as referring to the increasing influence of media in social, cultural, and political spheres (Deacon and Stanyer; Strömbäck and Esser; Shehata and Strömbäck). My own research into the influence of mediatisation on transport policy and projects in Sydney has centred more specifically on the influence of news media. My focus has been a trend towards news media influence in Australian politics and policy that has been observed by academics for more than a decade (Craig; Young; Ward, PR State; Ward, Public Affair; Ward, Power). My research entailed two case study projects, the failed Sydney CBD Metro (SCM) rail line and a North West Rail Link (NWR) currently under construction. Data-gathering included a news media study of 180 relevant print articles; 30 expert interviews with respondents from politics, the bureaucracy, transport planning, news media, and public relations, whose work related to transport (with a number working on the case study projects); and surveys, interviews, and focus groups with 149 public respondents. The research identified projects whose contrasting fortunes tell a significant story in relation to the influence of news media. The SCM, despite being a project deemed to be of considerable merit by the majority of expert respondents, was, as stated by a transport planner who worked on the project, “poorly sold,” which “turned it into a project that was very easy to ridicule.” Following a resulting period of intense news media criticism, the SCM was abandoned. As a transport reporter for a daily newspaper asserts in an interview, the prevailing view in the news media is that the project “was done on the back of an envelope.” According to experts with knowledge of the SCM, that years of planning had been undertaken was not properly presented to the public. Conversely, the experts I interviewed deem the NWR to be a low-priority project for Sydney. As a former chief of staff within both federal and state government departments including transport states, “if you are going to put money into anything in Sydney it would not be the NWR.” However, in the project’s favour is an overwhelming dominant public and media discourse that I label The north-west of Sydney is overdue rail transport. A communications respondent contends in an interview that because the NWR has “been talked about for so long” it holds “the right sighting, if you like, in people’s minds,” in other words, the media and the public have become used to the idea of the project.Ultimately, my findings, dealt with in more detail elsewhere (Richardson), suggest that powerful news media and public discourses, if not managed effectively, can be highly problematic for policymaking. This was found to be the case for the failure of the SCM. It is with this finding that I assert that the concept of curating the discourses surrounding a policy arena could hold considerable merit as a conceptual framework for discourse management. The Curatorial Turn in Policy Development? I was alerted to the idea of curating mediatised policy development during an expert interview for my empirical research. The respondent, chief editor of a Sydney newspaper, stated that, with an overwhelming mountain of information, news, views, and commentary being generated daily through the likes of the Internet and social media, the public needs curators to sift and sort the most important themes and arguments. The expert suggested this is now part of a journalist’s role. The idea of journalists as curators is far from new (Bakker 596). Nor is it the purpose of this paper. However, what struck me in this notion of curating was the critical role of sifting, sorting and ultimately selecting which themes, ideas, or pieces of information are privileged in myriad choices. My own empirical research was indicating that the management of highly influential news media and public discourses surrounding transport infrastructure also involved a considerable level of selection. Therefore, I hypothesised that the concept of curating might aid the managing of discourses when it comes to communicating for successful policy and project development that is subject to news media scrutiny. Research into scholarship has indicated that the concept of “the curatorial turn” is significant to this hypothesis. Since the 1960s the role of curator in art exhibition has shifted from that of “caretaker” for a collection to the shaper of an exhibition (O’Neill, “Turn”; O’Neill, Culture). Central to this shift is “the changing perception of the curator as carer to a curator who has a more creative and active part to play within the production of art itself” (O’Neill, Turn 243). Some commentators go so far as to suggest that curators have become cultural agents that “participate in the production of cultural value” (244). The curator’s role in exhibition design has also been equated to that of an author or auteur that drives an exhibition’s meaning (251–52). Why is this important for policy development? It is my view that there is certainly merit to viewing a significant part of the role of the political animal in policymaking as the curator of public and media discourse. As Beatrix Ruf suggests, the role of the curator is to create a “freedom for things to happen” within “a societal context” that not only takes into account the needs of the “artist” but also the “audience” (Bourriaud et al. 91). If we were to substitute bureaucrat for artist and media/public for audience then Ruf’s suggestion seems particularly relevant for the communication of policy. To return to Bourriaud’s quote that began this paper, perhaps the role of the curator/policymaker is not solely to produce a policy “but to invent, to fabricate, elaborate reading grids or coexistence grids,” to manage the discourses that influence the policy arena (Bourriaud et al. 92). Furthermore, the answer to why the concept of the curatorial turn seems relevant to policy development requires consideration not only of the rise of the voice and influence of the curator/policymaker but also of those at whose expense this shift has occurred. Through the rise of the curator the voice of the artist has dimmed. As the exhibition is elevated to “the status of quasi-artwork,” individual artworks themselves become simply “a useful fragment” (O’Neill, “Turn” 253). One of the underlying tensions of the curatorial turn is the rise of actors that are not practicing artists themselves. In other words, the producers of art, the artists, have less influence over their own practice. In New South Wales (NSW), we have witnessed a similar scenario with the steady rise of the voice and influence of the politician (and political adviser), at the expense of the public service. This loss of bureaucratic power was embedded structurally in the mid-1970s when Premier Neville Wran established the Ministerial Advisory Unit (MAU) to oversee NSW state government decisions. A respondent for my research states that when he began his career as a public servant: politicians didn’t really have a lot of ideas about things … the public service really ran the place … [Premier Wran] said, ‘this isn’t good enough. I’m being manipulated by the government departments. I’m going to set up something called the MAU which is politically appointed as a countervailing force to the bureaucracy to get the advice that I want.’The respondent infers a power grab by political actors to stymie the influence of the bureaucracy. This view is shared by several expert respondents for my research, as well as being substantiated by historian John Gunn (503). One of the clear results of the structural change has been that a politically driven media focus is now embedded in the structure of government policy and project decision-making. Instead of taking its lead from priorities emanating from the community, the bureaucracy is instead left with little choice but to look to the minister for guidance. As a project management consultant to government states in an interview:I think today the bureaucrat who makes the hard administrative decisions, the management decisions, is basically outweighed by communications, public relations, media relations director … the politicians are poll driven not policy driven. The respondent makes a point with which former politician Lindsay Tanner (Tanner) and academic Ian Ward (Ward, Power) agree—Australian politicians are increasingly structuring their operations around news media. The bureaucracy has become less relevant to policymaking as a result. My empirical research indicates this. The SCM and the NWR were highly publicised projects where the views of transport experts were largely ignored. They represent cases where the voice of the experts/artists had been completely suppressed by the voice of the politician/curator. I contend that this is where key questions of the role of the politician and the curator converge. Experts interviewed for my research express concerns that policymaking has been altered by structural changes to the bureaucracy. Similarly, some academics concerned with the rise of the curator question whether the shift will change the very nature of art (O’Neill, Cultures). A shared concern of the art world and those witnessing the policy arena in NSW is that the thoughts and ideas of those that do are being overshadowed by the views of those who talk. In terms of curatorial practice, O’Neill (Cultures) cites the views of Mick Wilson, who speaks of the rise of the “Foucauldian moment” and the “ubiquitous appeal of the term ‘discourse’ as a word to conjure and perform power,” where “even talking is doing something.” As O’Neill contends, “at this extreme, the discursive stands in the place of ‘doing’ within discourses on curatorial practice” (43). O’Neill submits Wilson’s point as an extreme view within the curatorial turn. However, the concern for the art world should be similar to the one experienced in the policy arena. Technical advice from the bureaucracy (doers) to ministers (talkers) has changed. In an interview with me, a partner in one of Australia’s leading architectural and planning practices contends that the technical advice of the bureaucracy to ministers is not as “fearless and robust” as it once was. Furthermore, he is concerned that planners have lost their influence as ministers now look to political advisers rather than technical advisers for direction. He states, “now what happens is most advisors to ministers are political advisers and they will give political advice … the planning advice hasn’t come from the planners.” The ultimate concern is that, through a silencing of the technical expert, policymaking is losing a vital layer of experience and knowledge that can only be to the detriment of the practice and its beneficiaries, the public. The closer one looks, the more evident the similarities between curating and policy development become. Acute budgetary limitations exist. There is an increased reliance on public funding. Large-scale curating, like policy development, involves “a negotiation of the relationship between public and private interests” (Ruf in Bourriaud et al. 90). There is also a tension between short- and long-term outlooks as well as local and global perspectives (Lunghi in Bourriaud et al. 97). And, significantly for my argument for the privileging of the concept of curating of discourse in policy, curating has also been called “a battlefield of ideas in which the public (or audience) has become ‘the big Other’” in that “everything that cannot find its audience, its public, is highly suspicious or very problematic” (Bourriaud in Bourriaud et al. 96–97). The closer the inspection, the starker the similarities of each pursuit. Lessons, Ramifications and Conclusions What can policymakers learn from the curatorial turn? For policymaking, it seems that the argumentative turn, the rise of news mediatisation, the strengthening of power and influence of the politician, and the “Foucauldian moment” have seen the rise of the discursive in place of doing that some quarters identify as being the case with the curatorial turn (O’Neill, Cultures). Therefore, it would be pertinent for policymakers to heed Bourriaud’s statement that began this paper: “the role of the curator is not to produce a concept of art (or policy) but to invent, to fabricate, elaborate reading grids or coexistence grids between them” (Bourriaud et al. 92). Is such a method of curating discourse the way forward for the political animal that seeks to achieve the politically “impossible” in policymaking? Perhaps for policymaking the importance of the concept of curating holds both opportunity and a warning. The opportunity, exemplified by the success of the NWR and the failure of the SCM projects in Sydney, is in accepting the role of media and public discourses in policy development so that they may be more thoroughly investigated and understood before being more effectively folded into the policymaking process. The warning lies in the concerns the curatorial turn has raised over the demise of the artist in light of the rise of discourse. The voice of the technical expert appears to be fading. How do we effectively curate discourses as well as restore the bureaucrat to former levels of robust fearlessness? I dare say it will take a political animal to do either. ReferencesBakker, Piet. “Mr Gates Returns.” Journalism Studies 15.5 (2014): 596–606.Bourriaud, Nicolas, Enrico Lunghi, Paul O’Neill, and Beatrix Ruf. “Is the Curator per Definition a Political Animal?” Rotterdam Dialogues: The Critics, the Curators, the Artists. Eds. Zoe Gray, Miriam Kathrein, Nicolaus Schafhausen, Monika Szewczyk, and Ariadne Urlus. Rotterdam: Witte de With Publishers, 2010. 87–99. Craig, Geoffrey. The Media, Politics and Public Life. Crows Nest, NSW: Allen and Unwin, 2004.Danta, Chris, and Dimitris Vardoulakis. “The Political Animal.” SubStance 37.3 (2008): 3–6. Dryzek, John S. “Policy Analysis and Planning: From Science to Argument.” The Argumentative Turn in Policy Analysis and Planning. Eds. Frank Fischer and John Forester. Durham, NC: Duke UP, 1993. 213–32.Fischer, Frank, and John Forester. “Editors’ Introduction.” The Argumentative Turn in Policy Analysis and Planning. Eds. Frank Fischer and John Forester. Durham, NC: Duke UP, 1993. 1–17.Fischer, Frank, and Herbert Gottweis. Argumentative Turn Revisited: Public Policy as Communicative Practice. Durham, NC: Duke UP, 2012.Gunn, John. Along Parallel Lines: A History of the Railways of New South Wales. Carlton: Melbourne UP, 1989.Majone, Giandomenico. Evidence, Argument, and Persuasion in the Policy Process. New Haven: Yale UP, 1989.O’Neill, Paul. “The Curatorial Turn: From Practice to Discourse.” The Biennial Reader. Eds. Elena Filipovic, Marieke Van Hal, and Solvig Øvstebø. Bergen, Norway: Bergen Kunsthall, 2007. 240–59.———. The Culture of Curating and the Curating of Cultures. Cambridge, MA: The MIT P, 2012.Richardson, Nicholas. “Political Upheaval in Australia: Media, Foucault and Shocking Policy.” Media International Australia. Forthcoming.Shehata, Adam, and Jesper Strömbäck. “Mediation of Political Realities: Media as Crucial Sources of Information.” Mediatization of Politics: Understanding the Transformation of Western Democracies. Eds. Frank Esser and Jesper Strömbäck. Basingstoke, Hampshire; New York, NY: Palgrave Macmillan, 2014. 93–112. Stone, Deborah. Policy Paradox and Political Reason. Glenview, Illinois: Scott, Foresman and Company, 1988.Strömbäck, Jesper, and Frank Esser. “Mediatization of Politics: Towards a Theoretical Framework.” Mediatization of Politics: Understanding the Transformation of Western Democracies. Eds. Frank Esser and Jesper Strömbäck. Basingstoke, Hampshire: Palgrave Macmillan, 2014. 3–28.Tanner, Lindsay. Sideshow: Dumbing Down Democracy. Carlton North, Victoria: Scribe, 2011.Throgmorton, James A. “Survey Research as Rhetorical Trope: Electric Power Planning in Chicago.” The Argumentative Turn in Policy Analysis and Planning. Eds. Frank Fischer and John Forester. Durham, NC: Duke UP, 1993. 117–44.Ward, Ian. “An Australian PR State?” Australian Journal of Communication 30.1 (2003): 25–42. ———. “Lobbying as a Public Affair: PR and Politics in Australia.” Communication, Creativity and Global Citizenship. ANZCA: Brisbane, 2009. 1039–56. ‹http://www.anzca.net/documents/anzca-09-1/refereed-proceedings-2009-1/79-lobbying-as-a-public-affair-pr-and-politics-in-australia-1/file.html›.———. “The New and Old Media, Power and Politics.” Government, Politics, Power and Policy in Australia. Eds. Dennis Woodward, Andrew Parkin, and John Summers. Frenchs Forest, NSW: Pearson, 2010. 374–93.Young, Sally. “Killing Competition: Restricting Access to Political Communication Channels in Australia.” AQ: Journal of Contemporary Analysis 75.3 (2003): 9–15.

Abstract Situated in the heart of the Tien Shan gold province, Unkurtash (3.5 Moz at 1.82 g/t) is a representative lode gold deposit that is hosted within the Carboniferous Andagul granodiorite in the Kassan district, western Kyrgyzstan. The Tien Shan gold province consists of porphyry and epithermal deposits, which are related to magmatic arcs, and lode gold deposits formed in the late stages of continent-continent collision that have been generally classified as mesothermal or orogenic type. Some of the lode gold deposits have been considered to be intrusion-related, but the genetic relationship between gold mineralization and the magmatic intrusions remains ambiguous in most cases due to lack of absolute timing of the gold mineralization. This paper addresses this problem through detailed geologic and petrographic studies of the Unkurtash gold deposit in conjunction with Re-Os, U-Pb, and 40Ar/39Ar dating along with S and Pb isotopes. The paragenesis of the Unkurtash deposit is divided into four stages. Stage 1 is related to pre-ore sheeted quartz veins outlined by narrow K-feldspar alteration envelopes. Stage 2 is characterized by quartz-molybdenite (±Au) veins with sericite and chlorite alteration assemblages. Stage 3 is the main gold mineralization stage and is characterized by gold-bearing quartz-ankerite veins and pervasive quartz ± K-feldspar ± rutile ± titanite alterations, with development of auriferous pyrite, free gold, electrum, galena, pyrrhotite, and minor chalcopyrite and arsenopyrite. Stage 4 is defined by the presence of abundant arsenopyrite in barren quartz-calcite veins associated with sericite ± muscovite ± carbonate alteration. Molybdenite from a single Stage 2 vein yielded a weighted mean Re-Os age of 306.5 ± 1.7 Ma (n = 7). Auriferous pyrite from Stage 3 yielded an Re-Os isochron age of 307.3 ± 8.0 Ma (n = 5) and a weighted mean age of 307.4 ± 3.1 Ma (n = 2; low-level highly radiogenic pyrite). 40Ar/39Ar ages of three hydrothermal K-feldspar samples from Stage 3 veins returned younger plateau ages (ca. 293–289 Ma) that are possibly related to post-ore thermal events. The molybdenite and pyrite Re-Os ages are comparable with a newly obtained U-Pb zircon age of 305.1 ± 2.7 Ma for the Andagul granodiorite, providing unequivocal evidence for synchronous gold mineralization and magmatism. The similarity in δ34SVienna-Canyon Diablo Troilite (V-CDT) between auriferous pyrite (5.7–7.1‰, n = 10) and the Andagul granodiorite (7.0–8.9‰, n = 4) and their similarity in Pb isotopes, which are significantly different from those of the pre-Silurian metamorphic rocks and regional Devonian sedimentary rocks, support the hypothesis that the Andagul granodiorite was the main source of metals and sulfur for mineralization. These results, together with concentric development of proximal skarn and metamorphic rock-hosted Au-As-Bi deposits and distal Sb-Au-As-Hg deposits around the Andagul intrusion, provide a strong case for an intrusion-related gold system. The establishment of an intrusion-related model for the Kassan district broadens the window for additional discoveries of gold deposits in the Tien Shan and elsewhere in the Central Asian orogenic belt.

The HIV proviral reservoir is the major barrier to cure. The predominantly replication-defective proviral landscape makes the measurement of virus that is likely to cause rebound upon ART-cessation challenging. To address this issue, novel assays to measure intact HIV proviruses have been developed. The Intact Proviral DNA Assay (IPDA) is a high-throughput assay that uses two probes to exclude the majority of defective proviruses and determine the frequency of intact proviruses, albeit without sequence confirmation. Quadruplex PCR with four probes (Q4PCR), is a lower-throughput assay that uses limiting dilution long distance PCR amplification followed by qPCR and near-full length genome sequencing (nFGS) to estimate the frequency of sequence-confirmed intact proviruses and provide insight into their clonal composition. To explore the advantages and limitations of these assays, we compared IPDA and Q4PCR measurements from 39 ART-suppressed people living with HIV. We found that IPDA and Q4PCR measurements correlated with one another but frequencies of intact proviral DNA differed by approximately 19-fold. This difference may be in part due to inefficiencies in long distance PCR amplification of proviruses in Q4PCR, leading to underestimates of intact proviral frequencies. In addition, nFGS analysis within Q4PCR explained that some of this difference is explained by proviruses that are classified as intact by IPDA but carry defects elsewhere in the genome. Taken together, this head-to-head comparison of novel intact proviral DNA assays provides important context for their interpretation in studies to deplete the HIV reservoir and shows that together the assays bracket true reservoir size. IMPORTANCE The Intact Proviral DNA Assay (IPDA) and Quadruplex PCR (Q4PCR) represent major advances in accurately quantifying and characterizing the replication competent HIV reservoir. This study compares the two novel approaches for measuring intact HIV proviral DNA in samples from 39 ART-suppressed people living with HIV, thereby informing ongoing efforts to deplete the HIV reservoir in cure-related trials.

Introduction: Evidence on the association between age at menopause and risk of dementia has been inconsistent. Some studies observed that later menopause was related to lower risk of dementia, while others reported no association, or even came to the opposite. Estradiol plays an important role in a wide range of neurological functions in brain, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative diseases, and accelerate the progression of dementia. Hypothesis: Based on the neuroprotective effects of estrogen, we hypothesized that earlier menopause might be related to higher risk of and earlier onset of dementia, compared with menopause at normal age or later. Methods: We used cohort data from UK Biobank and a total of 153 291 postmenopausal women were included. Age at menopause was categorized as <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-55, and >55 years. The main outcome was all-cause dementia, a comprehensive outcome including Alzheimer's disease (AD), vascular dementia (VD) and dementia classified elsewhere. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between menopausal age and all-cause dementia. We also stratified the age when dementia was diagnosed into ≤65 years and >65 years to explore the association between age at menopause and timing of experiencing dementia. All HRs were adjusted for age at last follow-up, race, education level, BMI, cigarette smoking, alcohol drinking, cardiovascular disease status, diabetes status, income, leisure activities and physical activities. We also used restricted cubic splines to analyze the dose-response relationship between menopausal age and dementia. Results: Among the 153 291 women, there were 1688 woman suffering from all-cause dementia. The average follow-up time was 11.7 years. Compared with menopausal age of 50-51 years, the HRs (95% CI) with dementia in women with menopausal age <40, 40-44, 45-49, 52-55 and >55 years were 1.53 (1.22-1.91), 1.07 (0.89-1.28), 1.08 (0.94-1.25), 0.81 (0.70-0.94), and 0.91 (0.78-1.06) respectively. Restricted cubic spline also showed an inverse dose-response relationship between them. In addition, compared to women with menopausal age of 50-51 years, women with early menopause (<45 years) had elevated risk of experiencing all-caused dementia before age 65 years (1.31, 1.07-1.72; P <0.001). Conclusions: Compared to women with menopausal age of 50-51 years, women with premature menopause (<40 years) had around 35% higher risk of having all-cause dementia, and women with early menopause (<45 years) were 1.3 times more likely to experience presenile dementia before age 65 years. Women with early menopause may need a close monitoring of their cognitive decline in clinical practice.

IntroductionTasmania hangs from the map of Australia like a drop in freefall from the substance of the mainland. Often the whole state is mislaid from Australian maps and logos (Reddit). Tasmania has, at least since federation, been considered peripheral—a region seen as isolated, a ‘problem’ economically, politically, and culturally. However, Tasmania not only cleaves to the ‘north island’ of Australia but is also subject to the gravitational pull of an even greater land mass—Antarctica. In this article, we upturn the political conventions of map-making that place both Antarctica and Tasmania in obscure positions at the base of the globe. We show how a changing global climate re-frames Antarctica and the Southern Ocean as key drivers of worldwide environmental shifts. The liquid and solid water between Tasmania and Antarctica is revealed not as a homogenous barrier, but as a dynamic and relational medium linking the Tasmanian archipelago with Antarctica. When Antarctica becomes the focus, the script is flipped: Tasmania is no longer on the edge, but core to a network of gateways into the southern land. The state’s capital of Hobart can from this perspective be understood as an “Antarctic city”, central to the geopolitics, economy, and culture of the frozen continent (Salazar et al.). Viewed from the south, we argue, Tasmania is not a problem, but an opportunity for a form of ecological, cultural, economic, and political sustainability that opens up the southern continent to science, discovery, and imagination.A Centre at the End of the Earth? Tasmania as ParadoxThe islands of Tasmania owe their existence to climate change: a period of warming at the end of the last ice age melted the vast sheets of ice covering the polar regions, causing sea levels to rise by more than one hundred metres (Tasmanian Climate Change Office 8). Eleven thousand years ago, Aboriginal people would have witnessed the rise of what is now called Bass Strait, turning what had been a peninsula into an archipelago, with the large island of Tasmania at its heart. The heterogeneous practices and narratives of Tasmanian regional identity have been shaped by the geography of these islands, and their connection to the Southern Ocean and Antarctica. Regions, understood as “centres of collective consciousness and sociospatial identities” (Paasi 241) are constantly reproduced and reimagined through place-based social practices and communications over time. As we will show, diverse and contradictory narratives of Tasmanian regionality often co-exist, interacting in complex and sometimes complementary ways. Ecocritical literary scholar C.A. Cranston considers duality to be embedded in the textual construction of Tasmania, writing “it was hell, it was heaven, it was penal, it was paradise” (29). Tasmania is multiply polarised: it is both isolated and connected; close and far away; rich in resources and poor in capital; the socially conservative birthplace of radical green politics (Hay 60). The weather, as if sensing the fine balance of these paradoxes, blows hot and cold at a moment’s notice.Tasmania has wielded extraordinary political influence at times in its history—notably during the settlement of Melbourne in 1835 (Boyce), and during protests against damming the Franklin River in the early 1980s (Mercer). However, twentieth-century historical and political narratives of Tasmania portray the Bass Strait as a barrier, isolating Tasmanians from the mainland (Harwood 61). Sir Bede Callaghan, who headed one of a long line of federal government inquiries into “the Tasmanian problem” (Harwood 106), was clear that Tasmania was a victim of its own geography:the major disability facing the people of Tasmania (although some residents may consider it an advantage) is that Tasmania is an island. Separation from the mainland adversely affects the economy of the State and the general welfare of the people in many ways. (Callaghan 3)This perspective may stem from the fact that Tasmania has maintained the lowest Gross Domestic Product per capita of all states since federation (Bureau of Infrastructure Transport and Regional Economics 9). Socially, economically, and culturally, Tasmania consistently ranks among the worst regions of Australia. Statistical comparisons with other parts of Australia reveal the population’s high unemployment, low wages, poor educational outcomes, and bad health (West 31). The state’s remoteness and isolation from the mainland states and its reliance on federal income have contributed to the whole of Tasmania, including Hobart, being classified as ‘regional’ by the Australian government, in an attempt to promote immigration and economic growth (Department of Infrastructure and Regional Development 1). Tasmania is indeed both regional and remote. However, in this article we argue that, while regionality may be cast as a disadvantage, the island’s remote location is also an asset, particularly when viewed from a far southern perspective (Image 1).Image 1: Antarctica (Orthographic Projection). Image Credit: Wikimedia Commons, Modified Shading of Tasmania and Addition of Captions by H. Nielsen.Connecting Oceans/Collapsing DistanceTasmania and Antarctica have been closely linked in the past—the future archipelago formed a land bridge between Antarctica and northern land masses until the opening of the Tasman Seaway some 32 million years ago (Barker et al.). The far south was tangible to the Indigenous people of the island in the weather blowing in from the Southern Ocean, while the southern lights, or “nuyina”, formed a visible connection (Australia’s new icebreaker vessel is named RSV Nuyina in recognition of these links). In the contemporary Australian imagination, Tasmania tends to be defined by its marine boundaries, the sea around the islands represented as flat, empty space against which to highlight the topography of its landscape and the isolation of its position (Davies et al.). A more relational geographic perspective illuminates the “power of cross-currents and connections” (Stratford et al. 273) across these seascapes. The sea country of Tasmania is multiple and heterogeneous: the rough, shallow waters of the island-scattered Bass Strait flow into the Tasman Sea, where the continental shelf descends toward an abyssal plain studded with volcanic seamounts. To the south, the Southern Ocean provides nutrient-rich upwellings that attract fish and cetacean populations. Tasmania’s coast is a dynamic, liminal space, moving and changing in response to the global currents that are driven by the shifting, calving and melting ice shelves and sheets in Antarctica.Oceans have long been a medium of connection between Tasmania and Antarctica. In the early colonial period, when the seas were the major thoroughfares of the world and inland travel was treacherous and slow, Tasmania’s connection with the Southern Ocean made it a valuable hub for exploration and exploitation of the south. Between 1642 and 1900, early European explorers were followed by British penal colonists, convicts, sealers, and whalers (Kriwoken and Williamson 93). Tasmania was well known to polar explorers, with expeditions led by Jules Dumont d’Urville, James Clark Ross, Roald Amundsen, and Douglas Mawson all transiting through the port of Hobart. Now that the city is no longer a whaling hub, growing populations of cetaceans continue to migrate past the islands on their annual journeys from the tropics, across the Sub-Antarctic Front and Antarctic circumpolar current, and into the south polar region, while southern species such as leopard seals are occasionally seen around Tasmania (Tasmania Parks and Wildlife). Although the water surrounding Tasmania and Antarctica is at times homogenised as a ‘barrier’, rendering these places isolated, the bodies of water that surround both are in fact permeable, and regularly crossed by both humans and marine species. The waters are diverse in their physical characteristics, underlying topography, sea life, and relationships, and serve to connect many different ocean regions, ecosystems, and weather patterns.Views from the Far SouthWhen considered in terms of its relative proximity to Antarctic, rather than its distance from Australia’s political and economic centres, Tasmania’s identity undergoes a significant shift. A sign at Cockle Creek, in the state’s far south, reminds visitors that they are closer to Antarctica than to Cairns, invoking a discourse of connectedness that collapses the standard ten-day ship voyage to Australia’s closest Antarctic station into a unit comparable with the routinely scheduled 5.5 hour flight to North Queensland. Hobart is the logistical hub for the Australian Antarctic Division and the French Institut Polaire Francais (IPEV), and has hosted Antarctic vessels belonging to the USA, South Korea, and Japan in recent years. From a far southern perspective, Hobart is not a regional Australian capital but a global polar hub. This alters the city’s geographic imaginary not only in a latitudinal sense—from “top down” to “bottom up”—but also a longitudinal one. Via its southward connection to Antarctica, Hobart is also connected east and west to four other recognized gateways: Cape Town in South Africa, Christchurch in New Zealand; Punta Arenas in Chile; and Ushuaia in Argentina (Image 2). The latter cities are considered small by international standards, but play an outsized role in relation to Antarctica.Image 2: H. Nielsen with a Sign Announcing Distances between Antarctic ‘Gateway’ Cities and Antarctica, Ushuaia, Argentina, 2018. Image Credit: Nicki D'Souza.These five cities form what might be called—to adapt geographer Klaus Dodds’ term—a ‘Southern Rim’ around the South Polar region (Dodds Geopolitics). They exist in ambiguous relationship to each other. Although the five cities signed a Statement of Intent in 2009 committing them to collaboration, they continue to compete vigorously for northern hemisphere traffic and the brand identity of the most prominent global gateway. A state government brochure spruiks Hobart, for example, as the “perfect Antarctic Gateway” emphasising its uniqueness and “natural advantages” in this regard (Tasmanian Government, 2016). In practice, the cities are automatically differentiated by their geographic position with respect to Antarctica. Although the ‘ice continent’ is often conceived as one entity, it too has regions, in both scientific and geographical senses (Terauds and Lee; Antonello). Hobart provides access to parts of East Antarctica, where the Australian, French, Japanese, and Chinese programs (among others) have bases; Cape Town is a useful access point for Europeans going to Dronning Maud Land; Christchurch is closest to the Ross Sea region, site of the largest US base; and Punta Arenas and Ushuaia neighbour the Antarctic Peninsula, home to numerous bases as well as a thriving tourist industry.The Antarctic sector is important to the Tasmanian economy, contributing $186 million (AUD) in 2017/18 (Wells; Gutwein; Tasmanian Polar Network). Unsurprisingly, Tasmania’s gateway brand has been actively promoted, with the 2016 Australian Antarctic Strategy and 20 Year Action Plan foregrounding the need to “Build Tasmania’s status as the premier East Antarctic Gateway for science and operations” and the state government releasing a “Tasmanian Antarctic Gateway Strategy” in 2017. The Chinese Antarctic program has been a particular focus: a Memorandum of Understanding focussed on Australia and China’s Antarctic relations includes a “commitment to utilise Australia, including Tasmania, as an Antarctic ‘gateway’.” (Australian Antarctic Division). These efforts towards a closer relationship with China have more recently come under attack as part of a questioning of China’s interests in the region (without, it should be noted, a concomitant questioning of Australia’s own considerable interests) (Baker 9). In these exchanges, a global power and a state of Australia generally classed as regional and peripheral are brought into direct contact via the even more remote Antarctic region. This connection was particularly visible when Chinese President Xi Jinping travelled to Hobart in 2014, in a visit described as both “strategic” and “incongruous” (Burden). There can be differences in how this relationship is narrated to domestic and international audiences, with issues of sovereignty and international cooperation variously foregrounded, laying the ground for what Dodds terms “awkward Antarctic nationalism” (1).Territory and ConnectionsThe awkwardness comes to a head in Tasmania, where domestic and international views of connections with the far south collide. Australia claims sovereignty over almost 6 million km2 of the Antarctic continent—a claim that in area is “roughly the size of mainland Australia minus Queensland” (Bergin). This geopolitical context elevates the importance of a regional part of Australia: the claims to Antarctic territory (which are recognised only by four other claimant nations) are performed not only in Antarctic localities, where they are made visible “with paraphernalia such as maps, flags, and plaques” (Salazar 55), but also in Tasmania, particularly in Hobart and surrounds. A replica of Mawson’s Huts in central Hobart makes Australia’s historic territorial interests in Antarctica visible an urban setting, foregrounding the figure of Douglas Mawson, the well-known Australian scientist and explorer who led the expeditions that proclaimed Australia’s sovereignty in the region of the continent roughly to its south (Leane et al.). Tasmania is caught in a balancing act, as it fosters international Antarctic connections (such hosting vessels from other national programs), while also playing a key role in administering what is domestically referred to as the Australian Antarctic Territory. The rhetoric of protection can offer common ground: island studies scholar Godfrey Baldacchino notes that as island narratives have moved “away from the perspective of the ‘explorer-discoverer-colonist’” they have been replaced by “the perspective of the ‘custodian-steward-environmentalist’” (49), but reminds readers that a colonising disposition still lurks beneath the surface. It must be remembered that terms such as “stewardship” and “leadership” can undertake sovereignty labour (Dodds “Awkward”), and that Tasmania’s Antarctic connections can be mobilised for a range of purposes. When Environment Minister Greg Hunt proclaimed at a press conference that: “Hobart is the gateway to the Antarctic for the future” (26 Apr. 2016), the remark had meaning within discourses of both sovereignty and economics. Tasmania’s capital was leveraged as a way to position Australia as a leader in the Antarctic arena.From ‘Gateway’ to ‘Antarctic City’While discussion of Antarctic ‘Gateway’ Cities often focuses on the economic and logistical benefit of their Antarctic connections, Hobart’s “gateway” identity, like those of its counterparts, stretches well beyond this, encompassing geological, climatic, historical, political, cultural and scientific links. Even the southerly wind, according to cartoonist Jon Kudelka, “has penguins in it” (Image 3). Hobart residents feel a high level of connection to Antarctica. In 2018, a survey of 300 randomly selected residents of Greater Hobart was conducted under the umbrella of the “Antarctic Cities” Australian Research Council Linkage Project led by Assoc. Prof. Juan Francisco Salazar (and involving all three present authors). Fourteen percent of respondents reported having been involved in an economic activity related to Antarctica, and 36% had attended a cultural event about Antarctica. Connections between the southern continent and Hobart were recognised as important: 71.9% agreed that “people in my city can influence the cultural meanings that shape our relationship to Antarctica”, while 90% agreed or strongly agreed that Hobart should play a significant role as a custodian of Antarctica’s future, and 88.4% agreed or strongly agreed that: “How we treat Antarctica is a test of our approach to ecological sustainability.” Image 3: “The Southerly” Demonstrates How Weather Connects Hobart and Antarctica. Image Credit: Jon Kudelka, Reproduced with Permission.Hobart, like the other gateways, activates these connections in its conscious place-branding. The city is particularly strong as a centre of Antarctic research: signs at the cruise-ship terminal on the waterfront claim that “There are more Antarctic scientists based in Hobart […] than at any other one place on earth, making Hobart a globally significant contributor to our understanding of Antarctica and the Southern Ocean.” Researchers are based at the Institute for Marine and Antarctic Studies (IMAS), the Commonwealth Scientific and Industrial Research Organisation (CSIRO), and the Australian Antarctic Division (AAD), with several working between institutions. Many Antarctic researchers located elsewhere in the world also have a connection with the place through affiliations and collaborations, leading journalist Jo Chandler to assert that “the breadth and depth of Hobart’s knowledge of ice, water, and the life forms they nurture […] is arguably unrivalled anywhere in the world” (86).Hobart also plays a significant role in Antarctica’s governance, as the site of the secretariats for the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) and the Agreement on the Conservation of Albatrosses and Petrels (ACAP), and as host of the Antarctic Consultative Treaty Meetings on more than one occasion (1986, 2012). The cultural domain is active, with Tasmanian Museum and Art Gallery (TMAG) featuring a permanent exhibit, “Islands to Ice”, emphasising the ocean as connecting the two places; the Mawson’s Huts Replica Museum aiming (among other things) to “highlight Hobart as the gateway to the Antarctic continent for the Asia Pacific region”; and a biennial Australian Antarctic Festival drawing over twenty thousand visitors, about a sixth of them from interstate or overseas (Hingley). Antarctic links are evident in the city’s natural and built environment: the dolerite columns of Mt Wellington, the statue of the Tasmanian Antarctic explorer Louis Bernacchi on the waterfront, and the wharfs that regularly accommodate icebreakers such as the Aurora Australis and the Astrolabe. Antarctica is figured as a southern neighbour; as historian Tom Griffiths puts it, Tasmanians “grow up with Antarctica breathing down their necks” (5). As an Antarctic City, Hobart mediates access to Antarctica both physically and in the cultural imaginary.Perhaps in recognition of the diverse ways in which a region or a city might be connected to Antarctica, researchers have recently been suggesting critical approaches to the ‘gateway’ label. C. Michael Hall points to a fuzziness in the way the term is applied, noting that it has drifted from its initial definition (drawn from economic geography) as denoting an access and supply point to a hinterland that produces a certain level of economic benefits. While Hall looks to keep the term robustly defined to avoid empty “local boosterism” (272–73), Gabriela Roldan aims to move the concept “beyond its function as an entry and exit door”, arguing that, among other things, the local community should be actively engaged in the Antarctic region (57). Leane, examining the representation of Hobart as a gateway in historical travel texts, concurs that “ingress and egress” are insufficient descriptors of Tasmania’s relationship with Antarctica, suggesting that at least discursively the island is positioned as “part of an Antarctic rim, itself sharing qualities of the polar region” (45). The ARC Linkage Project described above, supported by the Hobart City Council, the State Government and the University of Tasmania, as well as other national and international partners, aims to foster the idea of the Hobart and its counterparts as ‘Antarctic cities’ whose citizens act as custodians for the South Polar region, with a genuine concern for and investment in its future.Near and Far: Local Perspectives A changing climate may once again herald a shift in the identity of the Tasmanian islands. Recognition of the central role of Antarctica in regulating the global climate has generated scientific and political re-evaluation of the region. Antarctica is not only the planet’s largest heat sink but is the engine of global water currents and wind patterns that drive weather patterns and biodiversity across the world (Convey et al. 543). For example, Tas van Ommen’s research into Antarctic glaciology shows the tangible connection between increased snowfall in coastal East Antarctica and patterns of drought southwest Western Australia (van Ommen and Morgan). Hobart has become a global centre of marine and Antarctic science, bringing investment and development to the city. As the global climate heats up, Tasmania—thanks to its low latitude and southerly weather patterns—is one of the few regions in Australia likely to remain temperate. This is already leading to migration from the mainland that is impacting house prices and rental availability (Johnston; Landers 1). The region’s future is therefore closely entangled with its proximity to the far south. Salazar writes that “we cannot continue to think of Antarctica as the end of the Earth” (67). Shifting Antarctica into focus also brings Tasmania in from the margins. As an Antarctic city, Hobart assumes a privileged positioned on the global stage. This allows the city to present itself as central to international research efforts—in contrast to domestic views of the place as a small regional capital. The city inhabits dual identities; it is both on the periphery of Australian concerns and at the centre of Antarctic activity. Tasmania, then, is not in freefall, but rather at the forefront of a push to recognise Antarctica as entangled with its neighbours to the north.AcknowledgementsThis work was supported by the Australian Research Council under LP160100210.ReferencesAntonello, Alessandro. “Finding Place in Antarctica.” Antarctica and the Humanities. Eds. Peder Roberts, Lize-Marie van der Watt, and Adrian Howkins. London: Palgrave Macmillan, 2016. 181–204.Australian Government. 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This paper argues that artist Dope Saint Jude is transforming South African hip-hop by queering a genre that has predominantly been male and heteronormative. Specifically, I analyse the opening skit of her music video “Keep in Touch” in order to unpack the ways which she revives Gayle, a gay language that adopted double-coded forms of speech during the apartheid era—a context in which homosexuals were criminalised. The use of Gayle and spaces close to the city centre of Cape Town (such as Salt River and Woodstock) speaks to the city as it was before it was transformed by the decline of industries due to the country’s adoption of neoliberal economics and, more recently, by the gentrification of these spaces. Dope Saint Jude therefore reclaims these city spaces through her use of gay modes of speech that have a long history in Cape Town and by positioning her work as hip-hop, which has been popular in the city for well over two decades. Her inclusion of transgender MC and DJ Angel Ho pushes the boundaries of hegemonic and binary conceptions of gender identity even further. In essence, Dope Saint Jude is transforming local hip-hop in a context that is shaped significantly by US cultural imperialism. The artist is also transforming our perspective of spaces that have been altered by neoliberal economics.Setting the SceneDope Saint Jude (DSJ) is a queer MC from Elsies River, a working class township located on Cape Town's Cape Flats in South Africa. Elsies River was defined as a “coloured” neighbourhood under the apartheid state's Group Areas Act, which segregated South Africans racially. With the aid of the Population Registration Act, citizens were classified, not merely along the lines of white, Asian, or black—black subjects were also divided into further categories. The apartheid state also distinguished between black and “coloured” subjects. Michael MacDonald contends that segregation “ordained blacks to be inferior to whites; apartheid cast them to be indelibly different” (11). Apartheid declared “African claims in South Africa to be inferior to white claims” and effectively claimed that black subjects “belonged elsewhere, in societies of their own, because their race was different” (ibid). The term “coloured” defined people as “mixed race” to separate communities that might otherwise have identified as black in the broad and inclusive sense (Erasmus 16). Racial categorisation was used to create a racial hierarchy with white subjects at the top of that hierarchy and those classified as black receiving the least resources and benefits. This frustrated attempts to establish broad alliances of black struggles against apartheid. It is in this sense that race is socially and politically constructed and continues to have currency, despite the fact that biologically essentialist understandings of race have been discredited (Yudell 13–14). Thanks to apartheid town planning and resource allocation, many townships on the Cape Flats were poverty-stricken and plagued by gang violence (Salo 363). This continues to be the case because post-apartheid South Africa's embrace of neoliberal economics failed to address racialised class inequalities significantly (Haupt, Static 6–8). This is the '90s context in which socially conscious hip-hop crews, such as Prophets of da City or Black Noise, came together. They drew inspiration from Black Consciousness philosophy via their exposure to US hip-hop crews such as Public Enemy in order to challenge apartheid policies, including their racial interpellation as “coloured” as distinct from the more inclusive category, black (Haupt, “Black Thing” 178). Prophets of da City—whose co-founding member, Shaheen Ariefdien, also lived in Elsies River—was the first South African hip-hop outfit to record an album. Whilst much of their work was performed in English, they quickly transformed the genre by rapping in non-standard varieties of Afrikaans and by including MCs who rap in African languages (ibid). They therefore succeeded in addressing key issues related to race, language, and class disparities in relation to South Africa's transition to democracy (Haupt, “Black Thing”; Haupt, Stealing Empire). However, as is the case with mainstream US hip-hop, specifically gangsta rap (Clay 149), South African hip-hop has been largely dominated by heterosexual men. This includes the more commercial hip-hop scene, which is largely perceived to be located in Johannesburg, where male MCs like AKA and Cassper Nyovest became celebrities. However, certain female MCs have claimed the genre, notably EJ von Lyrik and Burni Aman who are formerly of Godessa, the first female hip-hop crew to record and perform locally and internationally (Haupt, Stealing Empire 166; Haupt, “Can a Woman in Hip-Hop”). DSJ therefore presents the exception to a largely heteronormative and male-dominated South African music industry and hip-hop scene as she transforms it with her queer politics. While queer hip-hop is not new in the US (Pabón and Smalls), this is new territory for South Africa. Writing about the US MC Jean Grae in the context of a “male-dominated music industry and genre,” Shanté Paradigm Smalls contends,Heteronormativity blocks the materiality of the experiences of Black people. Yet, many Black people strive for a heteronormative effect if not “reality”. In hip hop, there is a particular emphasis on maintaining the rigidity of categories, even if those categories fail [sic]. (87) DSJ challenges these rigid categories. Keep in TouchDSJ's most visible entry onto the media landscape to date has been her appearance in an H&M recycling campaign with British Sri Lankan artist MIA (H&M), some fashion shoots, her new EP—Reimagine (Dope Saint Jude)—and recent Finnish, US and French tours as well as her YouTube channel, which features her music videos. As the characters’ theatrical costumes suggest, “Keep in Touch” is possibly the most camp and playful music video she has produced. It commences somewhat comically with Dope Saint Jude walking down Salt River main road to a public telephone, where she and a young woman in pig tails exchange dirty looks. Salt River is located at the foot of Devil's Peak not far from Cape Town's CBD. Many factories were located there, but the area is also surrounded by low-income housing, which was designated a “coloured” area under apartheid. After apartheid, neighbourhoods such as Salt River, Woodstock, and the Bo-Kaap became increasingly gentrified and, instead of becoming more inclusive, many parts of Cape Town continued to be influenced by policies that enable racialised inequalities. Dope Saint Jude calls Angel Ho: DSJ: Awêh, Angie! Yoh, you must check this kak sturvy girl here by the pay phone. [Turns to the girl, who walks away as she bursts a chewing gum bubble.] Ja, you better keep in touch. Anyway, listen here, what are you wys?Angel Ho: Ah, just at the salon getting my hair did. What's good? DSJ: Wanna catch on kak today?Angel Ho: Yes, honey. But, first, let me Gayle you this. By the jol by the art gallery, this Wendy, nuh. This Wendy tapped me on the shoulder and wys me, “This is a place of decorum.”DSJ: What did she wys?Angel Ho: De-corum. She basically told me this is not your house. DSJ: I know you told that girl to keep in touch!Angel Ho: Yes, Mama! I'm Paula, I told that bitch, “Keep in touch!” [Points index finger in the air.](Saint Jude, Dope, “Keep in Touch”)Angel Ho's name is a play on the male name Angelo and refers to the trope of the ho (whore) in gangsta rap lyrics and in music videos that present objectified women as secondary to male, heterosexual narratives (Sharpley-Whiting 23; Collins 27). The queering of Angelo, along with Angel Ho’s non-binary styling in terms of hair, make-up, and attire, appropriates a heterosexist, sexualised stereotype of women in order to create room for a gender identity that operates beyond heteronormative male-female binaries. Angel Ho’s location in a hair salon also speaks to stereotypical associations of salons with women and gay subjects. In a discussion of gender stereotypes about hair salons, Kristen Barber argues that beauty work has traditionally been “associated with women and with gay men” and that “the body beautiful has been tightly linked to the concept of femininity” (455–56). During the telephonic exchange, Angel Ho and Dope Saint Jude code-switch between standard and non-standard varieties of English and Afrikaans, as the opening appellation, “Awêh,” suggests. In this context, the term is a friendly greeting, which intimates solidarity. “Sturvy” means pretentious, whilst “kak” means shit, but here it is used to qualify “sturvy” and means that the girl at the pay phone is very pretentious or “full of airs.” To be “wys” means to be wise, but it can also mean that you are showing someone something or educating them. The meanings of these terms shift, depending on the context. The language practices in this skit are in line with the work of earlier hip-hop crews, such as Prophets of da City and Brasse vannie Kaap, to validate black, multilingual forms of speech and expression that challenge the linguistic imperialism of standard English and Afrikaans in South Africa, which has eleven official languages (Haupt, “Black Thing”; Haupt, Stealing Empire; Williams). Henry Louis Gates’s research on African American speech varieties and literary practices emerging from the repressive context of slavery is essential to understanding hip-hop’s language politics. Hip-hop artists' multilingual wordplay creates parallel discursive universes that operate both on the syntagmatic axis of meaning-making and the paradigmatic axis (Gates 49; Haupt, “Stealing Empire” 76–77). Historically, these discursive universes were those of the slave masters and the slaves, respectively. While white hegemonic meanings are produced on the syntagmatic axis (which is ordered and linear), black modes of speech as seen in hip-hop word play operate on the paradigmatic axis, which is connotative and non-linear (ibid). Distinguishing between Signifyin(g) / Signification (upper case, meaning black expression) and signification (lower case, meaning white dominant expression), he argues that “the signifier ‘Signification’ has remained identical in spelling to its white counterpart to demonstrate [. . .] that a simultaneous, but negated, parallel discursive (ontological, political) universe exists within the larger white discursive universe” (Gates 49). The meanings of terms and expressions can change, depending on the context and manner in which they are used. It is therefore the shared experiences of speech communities (such as slavery or racist/sexist oppression) that determine the negotiated meanings of certain forms of expression. Gayle as a Parallel Discursive UniverseDSJ and Angel Ho's performance of Gayle takes these linguistic practices further. Viewers are offered points of entry into Gayle via the music video’s subtitles. We learn that Wendy is code for a white person and that to keep in touch means exactly the opposite. Saint Jude explains that Gayle is a very fun queer language that was used to kind of mask what people were saying [. . .] It hides meanings and it makes use of women's names [. . . .] But the thing about Gayle is it's constantly changing [. . .] So everywhere you go, you kind of have to pick it up according to the context that you're in. (Ovens, Saint Jude and Haupt)According to Kathryn Luyt, “Gayle originated as Moffietaal [gay language] in the coloured gay drag culture of the Western Cape as a form of slang amongst Afrikaans-speakers which over time, grew into a stylect used by gay English and Afrikaans-speakers across South Africa” (Luyt 8; Cage 4). Given that the apartheid state criminalised homosexuals, Gayle was coded to evade detection and to seek out other members of this speech community (Luyt 8). Luyt qualifies the term “language” by arguing, “The term ‘language’ here, is used not as a constructed language with its own grammar, syntax, morphology and phonology, but in the same way as linguists would discuss women’s language, as a way of speaking, a kind of sociolect” (Luyt 8; Cage 1). However, the double-coded nature of Gayle allows one to think of it as creating a parallel discursive universe as Gates describes it (49). Whereas African American and Cape Flats discursive practices function parallel to white, hegemonic discourses, gay modes of speech run parallel to heteronormative communication. Exclusion and MicroaggressionsThe skit brings both discursive practices into play by creating room for one to consider that DSJ queers a male-dominated genre that is shaped by US cultural imperialism (Haupt, Stealing Empire 166) as a way of speaking back to intersectional forms of marginalisation (Crenshaw 1244), which are created by “white supremacist capitalist patriarchy” (hooks 116). This is significant in South Africa where “curative rape” of lesbians and other forms of homophobic violence are prominent (cf. Gqola; Hames; Msibi). Angel Ho's anecdote conveys a sense of the extent to which black individuals are subject to scrutiny. Ho's interpretation of the claim that the gallery “is a place of decorum” is correct: it is not Ho's house. Black queer subjects are not meant to feel at home or feel a sense of ownership. This functions as a racial microaggression: “subtle insults (verbal, nonverbal, and/or visual) directed toward people of color, often automatically or unconsciously” (Solorzano, Ceja, and Yosso 60). This speaks to DSJ's use of Salt River, Woodstock, and Bo-Kaap for the music video, which features black queer bodies in performance—all of these spaces are being gentrified, effectively pushing working class people of colour out of the city (cf. Didier, Morange, and Peyroux; Lemanski). Gustav Visser explains that gentrification has come to mean a unit-by-unit acquisition of housing which replaces low-income residents with high-income residents, and which occurs independent of the structural condition, architecture, tenure or original cost level of the housing (although it is usually renovated for or by the new occupiers). (81–82) In South Africa this inequity plays out along racial lines because its neoliberal economic policies created a small black elite without improving the lives of the black working class. Instead, the “new African bourgeoisie, because it shares racial identities with the bulk of the poor and class interests with white economic elites, is in position to mediate the reinforcing cleavages between rich whites and poor blacks without having to make more radical changes” (MacDonald 158). In a news article about a working class Salt River family of colour’s battle against an eviction, Christine Hogg explains, “Gentrification often means the poor are displaced as the rich move in or buildings are upgraded by new businesses. In Woodstock and Salt River both are happening at a pace.” Angel Ho’s anecdote, as told from a Woodstock hair salon, conveys a sense of what Woodstock’s transformation from a coloured, working class Group Area to an upmarket, trendy, and arty space would mean for people of colour, including black, queer subjects. One could argue that this reading of the video is undermined by DSJ’s work with global brand H&M. Was she was snared by neoliberal economics? Perhaps, but one response is that the seeds of any subculture’s commercial co-option lie in the fact it speaks through commodities (for example clothing, make-up, CDs, vinyl, or iTunes / mp3 downloads (Hebdige 95; Haupt, Stealing Empire 144–45). Subcultures have a window period in which to challenge hegemonic ideologies before they are delegitimated or commercially co-opted. Hardt and Negri contend that the means that extend the reach of corporate globalisation could be used to challenge it from within it (44–46; Haupt, Stealing Empire 26). DSJ utilises her H&M work, social media, the hip-hop genre, and international networks to exploit that window period to help mainstream black queer identity politics.ConclusionDSJ speaks back to processes of exclusion from the city, which was transformed by apartheid and, more recently, gentrification, by claiming it as a creative and playful space for queer subjects of colour. She uses Gayle to lay claim to the city as it has a long history in Cape Town. In fact, she says that she is not reviving Gayle, but is simply “putting it on a bigger platform” (Ovens, Saint Jude, and Haupt). The use of subtitles in the video suggests that she wants to mainstream queer identity politics. Saint Jude also transforms hip-hop heteronormativity by queering the genre and by locating her work within the history of Cape hip-hop’s multilingual wordplay. ReferencesBarber, Kristin. “The Well-Coiffed Man: Class, Race, and Heterosexual Masculinity in the Hair Salon.” Gender and Society 22.4 (2008): 455–76.Cage, Ken. “An Investigation into the Form and Function of Language Used by Gay Men in South Africa.” Rand Afrikaans University: MA thesis, 1999.Clay, Andreana. “‘I Used to Be Scared of the Dick’: Queer Women of Color and Hip-Hop Masculinity.” Home Girls Make Some Noise: Hip Hop Feminism Anthology. Ed. Gwendolyn D. Pough, Elain Richardson, Aisha Durham, and Rachel Raimist. California: Sojourns, 2007.Collins, Patricia Hill. Black Sexual Politics: African Americans, Gender, and the New Racism. New York: Routledge, 2005. Crenshaw, Kimberle. “Mapping the Margins: Intersectionality, Identity Politics, and Violence against Women of Color”. Stanford Law Review 43.6 (1991): 1241–299.Didier, Sophie, Marianne Morange, and Elisabeth Peyroux. “The Adaptative Nature of Neoliberalism at the Local Scale: Fifteen Years of City Improvement Districts in Cape Town and Johannesburg.” Antipode 45.1 (2012): 121–39.Erasmus, Zimitri. “Introduction.” Coloured by History, Shaped by Place. Ed. Zimitri Erasmus. Cape Town: Kwela Books & SA History Online, 2001. Gates, Henry Louis. The Signifying Monkey: A Theory of Afro-American Literary Criticism. Oxford: Oxford UP, 1988.Gqola, Pumla Dineo. Rape: A South African Nightmare. Johannesburg: Jacana, 2015.Hames, Mary. “Violence against Black Lesbians: Minding Our Language.” Agenda 25.4 (2011): 87–91.Hardt, Michael, and Antonio Negri. Empire. London: Harvard UP, 2000.Haupt, Adam. “Can a Woman in Hip Hop Speak on Her Own Terms?” Africa Is a Country. 23 Mar. 2015. <http://africasacountry.com/2015/03/the-double-consciousness-of-burni-aman-can-a-woman-in-hip-hop-speak-on-her-own-terms/>.Haupt, Adam. Static: Race & Representation in Post-Apartheid Music, Media & Film. Cape Town: HSRC Press, 2012. Haupt, Adam. Stealing Empire: P2P, Intellectual Property and Hip-Hop Subversion. Cape Town: HSRC Press, 2008. Haupt, Adam. “Black Thing: Hip-Hop Nationalism, ‘Race’ and Gender in Prophets of da City and Brasse vannie Kaap.” Coloured by History, Shaped by Place. Ed. Zimitri Erasmus. Cape Town: Kwela Books & SA History Online, 2001. Hebdige, Dick. Subculture: The Meaning of Style. London: Routledge, 1979.Hogg, Christine. “In Salt River Gentrification Often Means Eviction: Family Set to Lose Their Home of 11 Years.” Ground Up. 15 June 2016. <http://www.groundup.org.za/article/salt-river-gentrification-often-means-eviction/>.hooks, bell. Outlaw: Culture: Resisting Representations. New York: Routledge, 1994.Lemanski, Charlotte. “Hybrid Gentrification in South Africa: Theorising across Southern and Northern Cities.” Urban Studies 51.14 (2014): 2943–60.Luyt, Kathryn. “Gay Language in Cape Town: A Study of Gayle – Attitudes, History and Usage.” University of Cape Town: MA thesis, 2014.MacDonald, Michael. Why Race Matters in South Africa. University of Kwazulu-Natal Press: Scottsville, 2006.Msibi, Thabo. “Not Crossing the Line: Masculinities and Homophobic Violence in South Africa”. Agenda. 23.80 (2009): 50–54.Pabón, Jessica N., and Shanté Paradigm Smalls. “Critical Intimacies: Hip Hop as Queer Feminist Pedagogy.” Women & Performance: A Journal of Feminist Theory (2014): 1–7.Salo, Elaine. “Negotiating Gender and Personhood in the New South Africa: Adolescent Women and Gangsters in Manenberg Township on the Cape Flats.” Journal of European Cultural Studies 6.3 (2003): 345–65.Solórzano, Daniel, Miguel Ceja, and Tara Yosso. “Critical Race Theory, Racial Microaggressions, and Campus Racial Climate: The Experiences of African American College Students.” Journal of Negro Education 69.1/2 (2000): 60–73.Sharpley-Whiting, T. Denean. Pimps Up, Ho’s Down: Hip Hop’s Hold on Young Black Women. New York: New York UP, 2007.Smalls, Shanté Paradigm. “‘The Rain Comes Down’: Jean Grae and Hip Hop Heteronormativity.” American Behavioral Scientist 55.1 (2011): 86–95.Visser, Gustav. “Gentrification: Prospects for Urban South African Society?” Acta Academica Supplementum 1 (2003): 79–104.Williams, Quentin E. “Youth Multilingualism in South Africa’s Hip-Hop Culture: a Metapragmatic Analysis.” Sociolinguistic Studies 10.1 (2016): 109–33.Yudell, Michael. “A Short History of the Race Concept.” Race and the Genetic Revolution: Science, Myth, and Culture. Ed. Sheldon Krimsky and Kathleen Sloan. New York: Columbia UP, 2011.InterviewsOvens, Neil, Dope Saint Jude, and Adam Haupt. One FM Radio interview. Cape Town. 21 Apr. 2016.VideosSaint Jude, Dope. “Keep in Touch.” YouTube. 23 Feb. 2015. <https://www.youtube.com/watch?v=w2ux9R839lE>. H&M. “H&M World Recycle Week Featuring M.I.A.” YouTube. 11 Apr. 2016. <https://www.youtube.com/watch?v=f7MskKkn2Jg>. MusicSaint Jude, Dope. Reimagine. 15 June 2016. <https://dopesaintjude.bandcamp.com/album/reimagine>.

This article aims to analyse an intercultural telephone invitation given by a Chinese tutor to an Australian student, and highlight general principles of intercultural invitations. This anecdote is based on a true story that took place in a university in Australia, but the persons' names used here are fictitious for the sake of confidentiality. Below is the transcript of the actual conversation between the Chinese tutor Dr Lin Liang (L) and his student Catherine Jones (C): C: Catherine speaking. L: Hi, Catherine, this is Lin. C: Hi, Teacher Lin. L: I would like to invite you to our New Year's party to be held in my house this Saturday evening. C: This Saturday? I am afraid I won't be able to make it because I am going to my best friend's birthday party. L: You know this is the end of our school year. It would be so nice for all of our classmates to gather together. C: But I have already promised my friend. L: En... It is a pity... C: Sorry about that, but -- L: Never mind. Enjoy your party then. C: Thanks. L: That's OK, bye. C: Bye. However, the story does not end here. About two hours later, Dr Lin rang Catherine a second time, asking if it was still possible for her to consider attending the Saturday party. Late in the evening around 9.00 pm, Dr Lin rang her yet again to invite her to the party, saying it would be OK even if she stayed just for a short while. The next day, Catherine lodged a complaint with the Dean, alleging that Dr. Lin's repeated calls constituted sexual harassment. Dr. Lin was highly distressed to learn of the complaint, and explained that he just wanted to indicate sincerity and warmth as required by an invitation, and had no other intentions. This communication breakdown invites a number of questions: What are the factors underlying Catherine's interpretation that Dr. Lin's repeated calls constituted sexual harassment? What are the factors underlying Dr. Lin's contention that his actions were intended to emphasise his sincerity? What factors would need to be recognised in order to facilitate culturally competent performances on both their parts? In order to answer these questions, this article will adopt a holistic approach based on an analytic framework encompassing three theoretical dimensions. This framework is comprised as follows: Differences in intercultural exchange and politeness behaviour; Aristotle's distinction between the three orientations of persuasive/rhetorical appeal; ethos, pathos, and logos; Austin and Searle's theory of speech acts, as applied to politeness behaviour and felicity conditions in communicative interaction as applied to the act of inviting. These approaches are conceptualised as three overlapping spheres, and their relatedness can be further illustrated: Figure 1 First and foremost, the case study in question is related to an intercultural interaction between the Australian and Chinese culture, and some research findings in relevant areas may help highlight the differences in politeness behaviour between high-context and low-context cultures (Hall). According to Hall, high-context cultures such as Chinese tend to stress the use of internalised or implicit message while low-context cultures tend to emphasise the use of explicit messages. In other words, in Chinese culture, the message may have some shared implied meanings that may go beyond the linguistic forms used in the message. Kaplan's model on oriental circularity and western linearity seemed to in accordance with Hall's model. Young's exploration of the directness and indirectness of American and Chinese requests further substantiated this point. In a similar way, differences may arise in determining the criteria for appropriate behaviour relating to the use of other directives across cultures. As Gao and Ting-Toomey suggest, Chinese culture seems to pay attention to qing (reciprocity and feelings of obligation) and guanxi (relationship building), while in low-context cultures such a stress tends to be missing. This difference may also help explain the differences in communicative patterns as discussed by Kaplan and Young. Zhu found that in making a sales offer, Chinese companies often try to establish a long-term relationship with their clients ("Structural Moves"). In contrast, Australian companies seem to mainly focus on promoting products. The stress on qing in Chinese culture may also be a crucial factor that contributes to the different criteria for a polite invitation as compared to the Australian culture. The following discussion will further explore the other two parameters (see Figure 1) the two cultures differ in when making an invitation, which may have finally led to the breakdown in communication between Dr. Lin and Catherine. As shown in Figure 1, the argument underpinning this approach is that a given illocutionary act reflects culture-specific preferences for certain persuasive/rhetorical orientations, thereby affecting the socio-linguistic performance, i.e. parole as opposed to langue (Cullen) related to politeness principles. In short, the persuasive/rhetorical orientation varies between cultures, which means that the nature of ostensibly equivalent illocutionary acts also varies. Consequently, cross-cultural competence will be limited unless one is aware of the rhetorical and politeness codes implicit in the performance of certain communicative actions. Note that rhetorical orientation may also influence the politeness behaviour directly as a specification of that orientation. This in turn requires an awareness of cultural preferences toward certain persuasive/rhetorical orientations. The interconnections between them and the theoretical utility of this approach will be made explicit in the course of this discussion. Austin and Searle conceptualise the speech acts as comprising of locution (langue) and illocution (parole). What is of vital importance is the illocutionary force of an utterance which is the performance of a speech act, such as an invitation. According to Searle, an invitation is a directive used to get the addressee to do something. Invitation can be understood as a particular form of persuasive speech act. It is generally intended to produce a particular response (i.e. acceptance). As an illocutionary action, an invitation seeks to establish a relationship of social expectations between the host and invitee. This requires certain felicity conditions to be met. In other words, for the speech act to be socially significant, it must create a shared sense of meaning in regard to some perceived change or modification to existing social relations. These are often so obvious that they require little explanation. However, felicity conditions in speech-acts are culture-specific and may include rhetorical and politeness devices that are not obvious to other cultures. Politeness behaviour in invitations, related to using appropriate language forms, is an important element in competent illocutionary performance. Leech contends that polite illocutions are likely to be seen as minimising the addressee's cost and maximising his/her benefits, and the opposite is true for the addresser. Politeness behaviour can also be further explained in the light of Brown and Levinson's face-saving theory. Many actions we perform with words are potential face-threatening acts, such as requests and invitations (Brown and Levinson). The addresser is thus often confronted with negative face wants and has to address them by applying Leech's principles, in which maximising the addressee's benefits is the dominant strategy to gain politeness. However, strategies to maximise the addressee's benefits can be culture-specific. This is further connected to the persuasive/rhetorical orientation. Based on Aristotle, the appeal from ethos emphasises the persuader's (host's) character and status or other social conventions which might oblige compliance. The appeal from pathos emphasises emotion/feelings (either positive or negative) in inducing the desired response. The appeal from logos emphasises reason and the logical consistency of the proposal with the ideas and motives of the persuadee (invitee). Moran and Stripp found that western cultures tend to have a logical orientation, while others such as Japanese and Chinese tend to be characterised by emotional or dogmatic orientations. In a similar manner, Chinese scholars seem to address ethos, logos and pathos at the same time, in particular the logos and pathos. These principles remain a well-accepted principle in Chinese writing theories. Li, for example, clearly explicates the persuasive principle in writing as qing li (the combination of the emotional and logical approaches). The explicitly preferred qing (feelings/emotions) can be seen as part of the Confucian values relating to harmony, consensus and relationship building as noted by Hofstede and Bond. The different rhetorical orientations are also further explored by Campbell. This difference may suggest that the preferred rhetorical orientations are also a key aspect underpinning competent illocutionary performance. For example in Chinese invitations, a stress on the emotional approach may validate behaviours such as repeating the invitation even after initial refusal. However, a stress on the logical orientation, such as in western cultures, may negate the validity of these politeness conditions. This clearly points out the necessity of understanding the criteria for competent performance across cultures. The felicity conditions of invitation in Euro-Australian culture require, first, that the potential host be in a legitimate position to offer hospitality, and second, that the potential guest be -- at least theoretically -- able and willing to accept. Thirdly, the locutionary form of politeness requires use of conventionally appropriate terms of address and wording. The illocutionary form requires that the host symbolically offer hospitality to the invitee without the imposition of charges or other demands. Furthermore, the implied benefit to the invitee would ideally be achieved though implied cost to the host (even if the invitee is addressed as if their presence constitutes the bestowal of a favour). Fourthly, depending on the nature of the relationship between the host and invitee, certain persuasive/rhetorical orientations are preferred over others (eg. an appeal to emotion may seem out of place in formal invitation). The initial invitation meets these criteria. Dr. Lin offers and Catherine declines, citing a plausible and legitimate reason for being unavailable. From Catherine's perspective, the felicity conditions for invitation are now redundant. She has already declined in a manner which makes it clear that she is socially obliged to be elsewhere. From a persuasive/rhetorical perspective, the first invitation was primarily based on an appeal from logos/reason. i.e. Dr. Lin did not know that Catherine had already committed herself to other plans and it would be reasonable to suppose that she might appreciate being invited to a social occasion. This was backed up by a secondary appeal from pathos/emotion, whereby Dr. Lin pointed out that it would be nice for the whole class to get together. However, the priority of attending a best friend's birthday-party over-rides both these appeals. In Euro-Australian culture, close personal friends enjoy greater social priority than classmates or more distant associates. For Dr. Lin, however, the politeness criteria for invitation were still applicable. From a Chinese cultural perspective, the illocutionary performance of invitation may require repetition of the offer, even if the initial approach has been declined. According to Zhu (Business Communication), in Chinese culture repeating invitations is an accepted ritual to indicate sincerity and hospitality. Thus in Dr. Lin's view the second approach is required to perform the illocutionary act competently. The persuasive appeal, however, has become oriented toward ethos, reflecting Chinese conventions pertaining to politeness behaviour. For Dr. Lin not to repeat the invitation might suggest that Catherine's presence was of merely casual concern. Therefore the sincerity of the invitation demanded the gesture of repetition, regardless of the logical grounds cited for the initial refusal. Unfortunately, Dr. Lin and Catherine perceive the second invitation in very different ways based on the illocutionary performance criteria of their respective cultures. For Catherine, the logical basis for her initial refusal renders Dr. Lin's performance incompetent, and creates uncertainty about his apparent motives. In Euro-Australian culture, the repeated invitation makes no logical sense, since a perfectly legitimate reason for declining has already been provided. Therefore the communicative action cannot be interpreted as an invitation. If it is, then it is performed in a culturally incompetent fashion which could legitimately be construed as pestering. Repeating an invitation which has already been declined may appear to be an emotional appeal. While an illocutionary invitation based on pathos conceivably may be competent in Euro-Australian culture, the only circumstances that it would occur in is between relatively close friends. The power-relations between Catherine, as student, and Dr. Lin, as tutor, precludes felicity in this case. Thus the same locutionary action is interpreted as two quite different illocutionary actions. This depends on the interpreter's culturally specific understanding of the social significance of the locution. Since Catherine's cultural conventions would implicitly deny the validity of a repeated invitation, the communicative action must be construed as something else. Catherine may have classified the repeated invitation as a minor issue of little consequence. However, when Dr. Lin called her up to invite her a third time, she interpreted the illocutionary act as harassment. From a contemporary Euro-Australian perspective, pestering may be irritating, but harassment is political in nature. Three factors lead Catherine to this conclusion. First, after two previous declinations, the third invitation could not fulfil the illocutionary performance criteria of a legitimate invitation. In particular, the persuasive/rhetorical orientation of the repeated appeals were not oriented toward logos, as befits the formality of the lecturer-student relation. Indeed, it was Dr. Lin's apparent attempt to approach Catherine in a non-formal manner (apparently oriented toward pathos rather than logos) which led her to this interpretation. Second, the fact that Dr. Lin' social status is higher than Catherine's introduced the problem of the implicit power-relations in the discourse. For Catherine, the third invitation was intrusive and pushy, and it seemed that her explanations had been ignored. The evening call demanded that she re-engage in the discourse of day-time student-tutor power-relations. Since she is subordinate to Dr. Lin, other strategies through which she might have asserted her rights may have carried the risk of subsequent disfavour. However, she obviously resented what she perceived as an attempt to inappropriately use status to interfere with her personal affairs and sought out higher authority to rectify the situation, hence the complaint of harassment made to the Dean. Ironically, Dr. Lin's third invitation in the evening may well have been intended to reduce the social distance between himself and Catherine created by workplace space-time power-relations. For Dr. Lin, the first invitation expressed the illocutionary intent. The second call made sure that the invitee was made to feel assured of the sincerity of the invitation, and the third ring expressed the would-be host's appreciation. Establishing a host-guest relationship is a key illocutionary function in Chinese invitation. Note though, that there may also be a 'face' consideration here. Dr. Lin attempts to facilitate Catherine's attendance by pointing out that it would be acceptable to attend for a brief period. This suggests a re-emphasis on the orientation to logos, since it points out a compromise which allows Catherine to attend both parties. It also allowed Dr. Lin to save 'face' by not having his invitation totally disregarded. However, it failed as an illocutionary performance because the felicity conditions for polite invitation had already been violated as far as Catherine was concerned, even though they remained intact throughout for Dr. Lin. In conclusion, it can be seen from the above analysis of the communication breakdown that persuasive orientations and politeness principles are interrelated and culturally sensitive. Euro-Australian culture stresses the logical orientation in illocutionary performance whereas Chinese culture seems to emphasise both the logical and emotional approaches. Without a recognition of this difference, specific politeness behaviours in intercultural invitations can lead to illocutionary incompetence. This has been exemplified by Catherine's misconstrual of Dr. Lin's intended invitation-performance as harassment. Therefore in intercultural communication, one ought not to judge a speech act such as an invitation based on one's own culture's felicity conditions. First and foremost, a basic understanding of persuasive orientations between cultures is essential. With appropriate understanding of these principles one can avoid misinterpreting the intent of the addresser, thus overcoming barriers in intercultural communication. Specifically, further appreciation of the interplay between rhetorical orientation, politeness codes and felicity conditions in illocutionary performances in different cultures is required for a fuller comprehension of potential cross-cultural incompetence. With this in mind, greater tolerance can be achieved, and intercultural competence enhanced. References Aristotle. Aristotle on Rhetoric: A Theory of Civic Discourse. Trans. George A. Kennedy. New York: Oxford UP, 1991. Austin, John. L. How to Do Things with Words. New York: Oxford UP, 1962. Brown, Penelope, and Stephen C. Levinson. Politeness: Some Universals in Language Usage. Cambridge, UK: Cambridge UP, 1987. Campbell, Charles. P. "Rhetorical Ethos: A Bridge between High-Context and Low-Context Cultures? The Cultural Context in Business Communication. Eds. Susanne Niemeier, Charles P. Campbell and René Dirven. Philadelphia: John Benjamins, 1998. 31-47. Cullen, Johnathan. Saussure. 2nd ed. London: Fontana, 1985. Ge Gao, and S. Ting-Toomey. Communicating Effectively with the Chinese. Thousand Oaks: Sage, 1998. Hall, E. T. Beyond Culture. Garden City, NY: Anchor, 1977. Hofstede, G., and M. H. Bond. "The Confucius Connection: From Cultural Roots to Economic Growth." Organisational Dynamics 16.4 (1988): 4-21. Kaplan, R. B. "Cultural Thought Patterns in Inter-Cultural Education." Language Learning 16 (1966): 1-20. Leech, Geoffery. Principles of Pragmatics. New York: Longman, 1983. Li Xiaoming. "Good Writing" in Cross-Cultural Context. Albany, NY: State U of New York P, 1996. Moran, R. T., and W. G. Stripp. Successful International Business Negotiations. Houston: Gulf, 1991. Searle, John R. Speech Acts: An Essay in the Philosophy of Language. Cambridge, UK: Cambridge UP, 1969. Young, Linda Wai Ling, ed. Crosstalk and Culture in Sino-American Communication. Cambridge, UK: Cambridge UP, 1994. Zhu Yunxia. Business Communication in China. New York: Nova Science Publishers, 1999. ---. Structural Moves Reflected in English and Chinese Sales Letters. Discourse Studies (In Press). Citation reference for this article MLA style: Zhu Yunxia, Peter Thompson. "Invitation or Sexual Harassment? An Analysis of an Intercultural Communication Breakdown." M/C: A Journal of Media and Culture 3.4 (2000). [your date of access] <http://www.api-network.com/mc/0008/invitation.php>. Chicago style: Zhu Yunxia, Peter Thompson, "Invitation or Sexual Harassment? An Analysis of an Intercultural Communication Breakdown," M/C: A Journal of Media and Culture 3, no. 4 (2000), <http://www.api-network.com/mc/0008/invitation.php> ([your date of access]). APA style: Zhu Yunxia, Peter Thompson. (2000) Invitation or sexual harassment? An analysis of an intercultural communication breakdown. M/C: A Journal of Media and Culture 3(4). <http://www.api-network.com/mc/0008/invitation.php> ([your date of access]).

As the distinction between disclosure-fuelled celebrity and lasting fame becomes difficult to discern, the “based on a true story” label has gained a particular traction among readers and viewers. This is despite much public approbation and private angst sometimes resulting from such disclosure as “little in the law or in society protects people from the consequences of others’ revelations about them” (Smith 537). Even fiction writers can stray into difficult ethical and artistic territory when they disclose the private facts of real lives—that is, recognisably biographical information—in their work, with autoethnographic fiction where authors base their fiction on their own lives (Davis and Ellis) not immune as this often discloses others’ stories (Ellis) as well. F. Scott Fitzgerald famously counselled writers to take their subjects from life and, moreover, to look to the singular, specific life, although this then had to be abstracted: “Begin with an individual, and before you know it, you find that you have created a type; begin with a type, and you find that you have created—nothing” (139). One of the problems when assessing fiction through this lens, however, is that, although many writers are inspired in their work by an actual life, event or historical period, the resulting work is usually ultimately guided by literary concerns—what writers often term the quest for aesthetic truth—rather than historical accuracy (Owen et al. 2008). In contrast, a biography is, and continues to be, by definition, an accurate account of a real persons’ life. Despite postmodern assertions regarding the relativity of truth and decades of investigation into the incorporation of fiction into biography, other non-fiction texts and research narratives (see, for instance: Wyatt), many biographers attest to still feeling irrevocably tied to the factual evidence in a way that novelists and the scriptors of biographically-based fictional television drama, movies and theatrical pieces do not (Wolpert; Murphy; Inglis). To cite a recent example, Louis Nowra’s Ice takes the life of nineteenth-century self-made entrepreneur and politician Malcolm McEacharn as its base, but never aspires to be classified as creative nonfiction, history or biography. The history in a historical novel is thus often, and legitimately, skewed or sidelined in order to achieve the most satisfying work of art, although some have argued that fiction may uniquely represent the real, as it is able to “play […] in the gap between the narratives of history and the actualities of the past” (Nelson n.p.). Fiction and non-fictional forms are, moreover, increasingly intermingling and intertwining in content and intent. The ugly word “faction” was an attempt to suggest that the two could simply be elided but, acknowledging wide-ranging debates about whether literature can represent the complexities of life with any accuracy and post-structuralist assertions that the idea of any absolute truth is outmoded, contemporary authors play with, and across, these boundaries, creating hybrid texts that consciously slide between invention and disclosure, but which publishers, critics and readers continue to define firmly as either fiction or biography. This dancing between forms is not particularly new. A striking example was Marion Halligan’s 2001 novel The Fog Garden which opens with a personal essay about the then recent death of her own much-loved husband. This had been previously published as an autobiographical memoir, “Cathedral of Love,” and again in an essay collection as “Lapping.” The protagonist of the novel is a recently widowed writer named Clare, but the inclusion of Halligan’s essay, together with the book’s marketing campaign which made much of the author’s own sadness, encourages readers to read the novel as a disclosure of the author’s own personal experience. This is despite Halligan’s attempt to keep the two separate: “Clare isn’t me. She’s like me. Some of her experience, terrors, have been mine. Some haven’t” (Fog Garden 9). In such acts of disclosure and denial, fiction and non-fiction can interrogate, test and even create each other, however quite vicious criticism can result when readers feel the boundaries demarking the two are breached. This is most common when authors admit to some dishonesty in terms of self-disclosure as can be seen, for instance, in the furore surrounding highly inflated and even wholly fabricated memoirs such as James Frey’s A Million Little Pieces, Margaret B. Jones’s Love and Consequences and Misha Defonseca’s A Mémoire of the Holocaust Years. Related problems and anxieties arise when authors move beyond incorporating and disclosing the facts of their own lives in memoir or (autobiographical) fiction, to using the lives of others in this way. Daphne Patai sums up the difference: “A person telling her life story is, in a sense, offering up her self for her own and her listener’s scrutiny […] Whether we should appropriate another’s life in this way becomes a legitimate question” (24–5). While this is difficult but seemingly manageable for non-fiction writers because of their foundational reliance on evidence, this anxiety escalates for fiction writers. This seems particularly extreme in relation to how audience expectations and prior knowledge of actual events can shape perceptions and interpretations of the resulting work, even when those events are changed and the work is declared to be one of fiction. I have discussed elsewhere, for instance, the difficult terrain of crafting fiction from well-known criminal cases (Brien, “Based on a True Story”). The reception of such work shows how difficult it is to dissociate creative product from its source material once the public and media has made this connection, no matter how distant that finished product may be from the original facts.As the field of biography continues to evolve for writers, critics and theorists, a study of one key text at a moment in that evolution—Jill Shearer’s play Georgia and its reliance on disclosing the life of artist Georgia O’Keeffe for its content and dramatic power—reveals not only some of the challenges and opportunities this close relationship offers to the writers and readers of life stories, but also the pitfalls of attempting to dissemble regarding artistic intention. This award-winning play has been staged a number of times in the past decade but has attracted little critical attention. Yet, when I attended a performance of Georgia at La Boite Theatre in Brisbane in 1999, I was moved by the production and admiring of Shearer’s writing which was, I told anyone who would listen, a powerfully dramatic interpretation of O’Keeffe’s life, one of my favourite artists. A full decade on, aspects of the work and its performance still resonate through my thinking. Author of more than twenty plays performed throughout Australia and New Zealand as well as on Broadway, Shearer was then (and is) one of Australia’s leading playwrights, and I judged Georgia to be a major, mature work: clear, challenging and confident. Reading the Currency Press script a year or so after seeing the play reinforced for me how distinctive and successful a piece of theatre Shearer had created utilising a literary technique which has been described elsewhere as fictionalised biography—biography which utilises fictional forms in its presentation but stays as close to the historical record as conventional biography (Brien, The Case of Mary Dean).The published version of the script indeed acknowledges on its title page that Georgia is “inspired by the later life of the American artist Georgia O’Keeffe” (Shearer). The back cover blurb begins with a quote attributed to O’Keeffe and then describes the content of the play entirely in terms of biographical detail: The great American artist Georgia O’Keeffe is physically, emotionally and artistically debilitated by her failing eyesight. Living amidst the Navajo spiritual landscape in her desert home in New Mexico, she becomes prey to the ghosts of her past. Her solitude is broken by Juan, a young potter, whose curious influence on her life remains until her death at 98 (Georgia back cover). This short text ends by unequivocally reinforcing the relation between the play and the artist’s life: “Georgia is a passionate play that explores with sensitivity and wry humour the contradictions and the paradoxes of the life of Georgia O’Keeffe” (Georgia back cover). These few lines of plot synopsis actually contain a surprisingly large number of facts regarding O’Keeffe’s later life. After the death of her husband (the photographer and modern art impresario Alfred Steiglitz whose ghost is a central character in the play), O’Keeffe did indeed relocate permanently to Abiquiú in New Mexico. In 1971, aged 84, she was suffering from an irreversible degenerative disease, had lost her central vision and stopped painting. One autumn day in 1973, Juan Hamilton, a young potter, appeared at her adobe house looking for work. She hired him and he became her lover, closest confidante and business manager until her death at 98. These facts form not only the background story but also much of the riveting content for Georgia which, as the published script’s introduction states, takes as its central themes: “the dilemma of the artist as a an older woman; her yearning to create against the fear of failing artistic powers; her mental strength and vulnerability; her sexuality in the face of physical deterioration; her need for companionship and the paradoxical love of solitude” (Rider vii). These issues are not only those which art historians identify as animating the O’Keeffe’s later life and painting, but ones which are discussed at length in many of the biographies of the artist published from 1980 to 2007 (see, for instance: Arrowsmith and West; Berry; Calloway and Bry; Castro; Drohojowska-Philp; Eisler; Eldredge; Harris; Hogrefe; Lisle; Peters; Reily; Robinson).Despite this clear focus on disclosing aspects of O’Keeffe’s life, both the director’s and playwright’s notes prefacing the published script declare firmly that Georgia is fiction, not biography. While accepting that these statements may be related to copyright and privacy concerns, the stridency of the denials of the biography label with its implied intention of disclosing the facts of a life, are worthy of analysis. Although noting that Georgia is “about the American artist Georgia O’Keeffe”, director of the La Boite production Sue Rider asserts that not only that the play moves “beyond the biographical” (vii) but, a few pages later, that it is “thankfully not biography” (xii). This is despite Rider’s own underscoring of the connection to O’Keeffe by setting up an exhibition of the artist’s work adjacent to the theatre. Shearer, whose research acknowledgments include a number of works about O’Keeffe, is even more overtly strident in her denial of any biographical links stating that her characters, “this Juan, Anna Marie and Dorothy Norman are a work of dramatic fiction, as is the play, and should be taken as such” (xiii).Yet, set against a reading of the biographies of the artist, including those written in the intervening decade, Georgia clearly and remarkably accurately discloses the tensions and contradictions of O’Keeffe’s life. It also draws on a significant amount of documented biographical data to enhance the dramatic power of what is disclosed by the play for audiences with this knowledge. The play does work as a coherent narrative for a viewer without any prior knowledge of O’Keeffe’s life, but the meaning of the dramatic action is enhanced by any biographical knowledge the audience possesses. In this way, the play’s act of disclosure is reinforced by this externally held knowledge. Although O’Keeffe’s oeuvre is less well known and much anecdotal detail about her life is not as familiar for Australian viewers as for those in the artist’s homeland, Shearer writes for an international as well as an Australian audience, and the program and adjacent exhibition for the Brisbane performance included biographical information. It is also worth noting that large slabs of biographical detail are also omitted from the play. These omissions to disclosure include O’Keeffe’s early life from her birth in 1887 in Wisconsin to her studies in Chicago and New York from 1904 to 1908, as well as her work as a commercial artist and art teacher in Texas and other Southern American states from 1912 to 1916. It is from this moment in 1916, however, that the play (although opening in 1946) constructs O’Keeffe’s life right through to her death in 1986 by utilising such literary devices as flashbacks, dream sequences and verbal and visual references.An indication of the level of accuracy of the play as biographical disclosure can be ascertained by unpacking the few lines of opening stage directions, “The Steiglitz’s suite in the old mid-range Shelton Hotel, New York, 1946 ... Georgia, 59, in black, enters, dragging a coffin” (1). In 1946, when O’Keeffe was indeed aged 59, Steiglitz died. The couple had lived part of every year at the Shelton Towers Hotel at 525 Lexington Avenue (now the New York Marriott East Side), a moderately priced hotel made famous by its depiction in O’Keeffe’s paintings and Steiglitz’s photographs. When Stieglitz suffered a cerebral thrombosis, O’Keeffe was spending the summer in New Mexico, but she returned to New York where her husband died on 13 July. This level of biographical accuracy continues throughout Georgia. Halfway through the first page “Anita, 52” enters. This character represents Anita Pollitzer, artist, critic and O’Keeffe’s lifelong friend. The publication of her biography of O’Keeffe, A Woman on Paper, and Georgia’s disapproval of this, is discussed in the play, as are their letters, which were collected and published in 1990 as Lovingly, Georgia (Gibiore). Anita’s first lines in the play after greeting her friend refer to this substantial correspondence: “You write beautifully. I always tell people: “I have a friend who writes the most beautiful letters” (1). In the play, as in life, it is Anita who introduces O’Keeffe’s work to Stieglitz who is, in turn, accurately described as: “Gallery owner. Two Nine One, Fifth Avenue. Leader of the New York avant-garde, the first to bring in the European moderns” (6). The play also chronicles how (unknown to O’Keeffe) Steiglitz exhibited the drawings Pollitzer gave him under the incorrect name, a scene which continues with Steiglitz persuading Georgia to allow her drawings to remain in his gallery (as he did in life) and ends with a reference to his famous photographs of her hands and nude form. Although the action of a substantial amount of real time is collapsed into a few dramatic minutes and, without doubt, the dialogue is invented, this invention achieves the level of aesthetic truth aimed for by many contemporary biographers (Jones)—as can be assessed when referring back to the accepted biographical account. What actually appears to have happened was that, in the autumn 1915, while teaching art in South Carolina, O’Keeffe was working on a series of abstract charcoal drawings that are now recognised as among the most innovative in American art of that time. She mailed some of these drawings to Pollitzer, who showed them Steiglitz, who exhibited ten of them in April 1916, O’Keeffe only learning of this through an acquaintance. O’Keeffe, who had first visited 291 in 1908 but never spoken to Stieglitz, held his critical opinion in high regard, and although confronting him over not seeking her permission and citing her name incorrectly, eventually agreed to let her drawings hang (Harris). Despite Shearer’s denial, the other characters in Georgia are also largely biographical sketches. Her “Anna Marie”, who never appears in the play but is spoken of, is Juan’s wife (in real life Anna Marie Hamilton), and “Dorothy Norman” is the character who has an affair with Steiglitz—the discovery of which leads to Georgia’s nervous breakdown in the play. In life, while O’Keeffe was in New Mexico, Stieglitz became involved with the much younger Norman who was, he claimed, only his gallery assistant. When O’Keeffe discovered Norman posing nude for her husband (this is vividly imagined in Georgia), O’Keeffe moved out of the Shelton and suffered from the depression that led to her nervous breakdown. “ Juan,” who ages from 26 to 39 in the play, represents the potter Juan Hamilton who encouraged the nearly blind O’Keeffe to paint again. In the biographical record there is much conjecture about Hamilton’s motives, and Shearer sensitively portrays her interpretation of this liaison and the difficult territory of sexual desire between a man and a much older woman, as she also too discloses the complex relationship between O’Keeffe and the much older Steiglitz.This complexity is described through the action of the play, but its disclosure is best appreciated if the biographical data is known. There are also a number of moments of biographical disclosure in the play that can only be fully understood with biographical knowledge in hand. For instance, Juan refers to Georgia’s paintings as “Beautiful, sexy flowers [... especially] the calla lilies” (24). All attending the play are aware (from the exhibition, program and technical aspects of the production) that, in life, O’Keeffe was famous for her flower paintings. However, knowing that these had brought her fame and fortune early in her career with, in 1928, a work titled Calla Lily selling for U.S. $25,000, then an enormous sum for any living American artist, adds to the meaning of this line in the play. Conversely, the significant level of biographical disclosure throughout Georgia does not diminish, in any way, the power or integrity of Shearer’s play as a literary work. Universal literary (and biographical) themes—love, desire and betrayal—animate Georgia; Steiglitz’s spirit haunts Georgia years after his death and much of the play’s dramatic energy is generated by her passion for both her dead husband and her younger lover, with some of her hopeless desire sublimated through her relationship with Juan. Nadia Wheatley reads such a relationship between invention and disclosure in terms of myth—relating how, in the process of writing her biography of Charmain Clift, she came to see Clift and her husband George Johnson take on a larger significance than their individual lives: “They were archetypes; ourselves writ large; experimenters who could test and try things for us; legendary figures through whom we could live vicariously” (5). In this, Wheatley finds that “while myth has no real beginning or end, it also does not bother itself with cause and effect. Nor does it worry about contradictions. Parallel tellings are vital to the fabric” (5). In contrast with both Rider and Shearer’s insistence that Georgia was “not biography”, it could be posited that (at least part of) Georgia’s power arises from the creation of such mythic value, and expressly through its nuanced disclosure of the relevant factual (biographical) elements in parallel to the development of its dramatic (invented) elements. Alongside this, accepting Georgia as such a form of biographical disclosure would mean that as well as a superbly inventive creative work, the highly original insights Shearer offers to the mass of O’Keeffe biography—something of an American industry—could be celebrated, rather than excused or denied. ReferencesArrowsmith, Alexandra, and Thomas West, eds. Georgia O’Keeffe & Alfred Stieglitz: Two Lives—A Conversation in Paintings and Photographs. Washington DC: HarperCollins and Calloway Editions, and The Phillips Collection, 1992.Berry, Michael. Georgia O’Keeffe. New York: Chelsea House, 1988.Brien, Donna Lee. The Case of Mary Dean: Sex, Poisoning and Gender Relations in Australia. Unpublished PhD Thesis. Queensland University of Technology, 2004. –––. “‘Based on a True Story’: The Problem of the Perception of Biographical Truth in Narratives Based on Real Lives”. TEXT: Journal of Writers and Writing Programs 13.2 (Oct. 2009). 19 Oct. 2009 < http://www.textjournal.com.au >.Calloway, Nicholas, and Doris Bry, eds. Georgia O’Keeffe in the West. New York: Knopf, 1989.Castro, Jan G. The Art and Life of Georgia O’Keeffe. New York: Crown Publishing, Random House, 1985.Davis, Christine S., and Carolyn Ellis. “Autoethnographic Introspection in Ethnographic Fiction: A Method of Inquiry.” In Pranee Liamputtong and Jean Rumbold, eds. Knowing Differently: Arts-Based and Collaborative Research. New York: Nova Science, 2008. 99–117.Defonseca, Misha. Misha: A Mémoire of the Holocaust Years. Bluebell, PA: Mt. Ivy Press, 1997.Drohojowska-Philp, Hunter. Full Bloom: The Art and Life of Georgia O’Keeffe. New York: WW Norton, 2004.Ellis, Carolyn. “Telling Secrets, Revealing Lives: Relational Ethics in Research with Intimate Others.” Qualitative Inquiry 13.1 (2007): 3–29. Eisler, Benita. O’Keeffe and Stieglitz: An American Romance. New York: Doubleday, 1991.Eldredge, Charles C. Georgia O’Keeffe: American and Modern. New Haven: Yale UP, 1993.Fitzgerald, F. Scott. The Diamond as Big as the Ritz and Other Stories. Harmondsworth, U.K.: Penguin, 1962.Frey, James. A Million Little Pieces. New York: N.A. Talese/Doubleday, 2003.Gibiore, Clive, ed. Lovingly, Georgia. New York: Simon and Schuster, 1990.Halligan, Marion. “Lapping.” In Peter Craven, ed. Best Australian Essays. Melbourne: Bookman P, 1999. 208–13.Halligan, Marion. The Fog Garden. Sydney: Allen and Unwin, 2001.Halligan, Marion. “The Cathedral of Love.” The Age 27 Nov. 1999: Saturday Extra 1.Harris, J. C. “Georgia O’Keeffe at 291”. Archives of General Psychiatry 64.2 (Feb. 2007): 135–37.Hogrefe, Jeffrey. O’Keeffe: The Life of an American Legend. New York: Bantam, 1994.Inglis, Ian. “Popular Music History on Screen: The Pop/Rock Biopic.” Popular Music History 2.1 (2007): 77–93.Jones, Kip. “A Biographic Researcher in Pursuit of an Aesthetic: The Use of Arts-Based (Re)presentations in “Performative” Dissemination of Life Stories”. Qualitative Sociology Review 2.1 (Apr. 2006): 66–85. Jones, Margaret B. Love and Consequences: A Memoir of Hope and Survival. New York: Riverhead Books, 2008.Lisle, Laurie. Portrait of an Artist: A Biography of Georgia O’Keeffe. New York: Seaview Books, 1980.Murphy, Mary. “Limited Lives: The Problem of the Literary Biopic”. Kinema 17 (Spr. 2002): 67–74. Nelson, Camilla. “Faking It: History and Creative Writing.” TEXT: Journal of Writing and Writing Courses 11.2 (Oct. 2007). 19 Oct. 2009 < http://www.textjournal.com.au/oct07/nelson.htm >.Nowra, Louis. Ice. Crows Nest: Allen and Unwin, 2008.Owen, Jillian A. Tullis, Chris McRae, Tony E. Adams, and Alisha Vitale. “Truth Troubles.” Qualitative Inquiry 15.1 (2008): 178–200.Patai, Daphne. “Ethical Problems of Personal Narratives, or, Who Should Eat the Last Piece of Cake.” International Journal of Oral History 8 (1987): 5–27.Peters, Sarah W. Becoming O’Keeffe. New York: Abbeville Press, 1991.Pollitzer, Anita. A Woman on Paper. New York: Simon and Schuster, 1988.Reily, Nancy Hopkins. Georgia O’Keeffe. A Private Friendship, Part II. Santa Fe, NM: Sunstone Press, 2009.Rider, Sue. “Director’s Note.” Georgia [playscript]. Sydney: Currency Press, 2000. vii–xii.Robinson, Roxana. Georgia O’Keeffe: A Life. London: Bloomsbury Publishing, 1990. Shearer, Jill. Georgia [playscript]. Sydney: Currency Press, 2000.Smith, Thomas R. “How Our Lives Become Stories: Making Selves [review]”. Biography 23.3 (2000): 534–38.Wheatley, Nadia. The Life and Myth of Charmian Clift. Sydney: Flamingo, 2001.Wolpert, Stanley. “Biography as History: A Personal Reflection”. Journal of Interdisciplinary History 40.3 (2010): 399–412. Pub. online (Oct. 2009). 19 Oct. 2009 < http://www.mitpressjournals.org/toc/jinh/40/3 >.Wyatt, Jonathan. “Research, Narrative and Fiction: Conference Story”. The Qualitative Report 12.2 (Jun. 2007): 318–31.

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus. Methodology: Twenty-eight Wistar Albino rats were randomised into four groups as control (C), diabetic (DC), diabetic with hepatic ischemia-reperfusion injury (DIR), and diabetic but administered dexmedetomidine followed by hepatic IRI (DIRD) groups. Hepatic tissue samples were evaluated histopathologically by semiquantitative methods. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathion s-transpherase (GST), and catalase (CAT) enzyme levels were investigated in liver and kidney tissues as oxidative state parameters. Results: In Group DIR; hepatocyte degeneration, sinusoidal dilatation, pycnotic nucleus, and necrotic cells were found to be more in rat hepatic tissue; while mononuclear cell infiltration was higher in the parenchyme. MDA levels were significantly lower; but SOD levels were significantly higher in Group DIRD with regard to Group DIR. In the IRI induced diabetic rats’ hepatic and nephrotic tissues MDA levels, showing oxidative injury, were found to be lower. SOD levels, showing early antioxidant activity, were higher. Conclusion: The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease IRI. Key words: Hepatic ischemia reperfusion injury; Diabetes mellitus; Dexmedetomidine; Rat; MDA; SOD Citation: Sezen SC, Işık B, Bilge M, Arslan M, Çomu FM, Öztürk L, Kesimci E, Kavutçu M. Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats. Anaesth Pain & Intensive Care 2016;20(2):143-149 Received: 21 November 2015; Reviewed: 10, 24 December 2015, 9, 10 June 2016; Corrected: 12 December 2015; Accepted: 10 June 2016 INTRODUCTİON Perioperative acute tissue injury induced by ischemia-reperfusion is a comman clinical event caused by reduced blood supply to the tissue being compromised during major surgery. Ischemia leads to cellular injury by depleting cellular energy deposits and resulting in accumulation of toxic metabolites. The reperfusion of tissues that have remained in ischemic conditions causes even more damage.1 Furthermore hepatic ischemia-reperfusion injury (IRI) demonstrates a strong relationship with peri-operative acute kidney injury.2 The etiology of diabetic complications is strongly associated with increased oxidative stress (OS). Diabetic patients are known to have a high risk of developing OS or IRI which results with tissue failure.3 The most important role in ischemia and reperfusion is played by free oxygen radicals.1 In diabetes, characterized by hyperglycemia, even more free oxygen radicals are produced due to oxidation of glucose and glycosylation of proteins.3 The structures which are most sensitive to free oxygen radicals in the cells are membrane lipids, proteins, nucleic acids and deoxyribonucleic acids.1 It has been reported that endogenous antioxidant enzymes [superoxide dismutase (SOD), glutathion s-transpherase (GST), catalase (CAT)] play an important role to alleviate IRI.4-8 Also some pharmacological agents have certain effects on IRI.1 The anesthetic agents influence endogenous antioxidant systems and free oxygen radical formation.9-12 Dexmedetomidine is a selective α-2 adrenoceptor agonist agent. It has been described as a useful and safe adjunct in many clinical applications. It has been found that it may increase urine output by considerably redistributing cardiac output, inhibiting vasopressin secretion and maintaining renal blood flow and glomerular filtration. Previous studies demonstrated that dexmedetomidine provides protection against renal, focal cerebral, cardiac, testicular, and tourniquet-induced IRI.13-18 Arslan et al observed that dexmedetomidine protected against lipid peroxidation and cellular membrane alterations in hepatic IRI, when given before induction of ischemia.17 Si et al18 demonstrated that dexmedetomidine treatment results in a partial but significant attenuation of renal demage induced by IRI through the inactivation of JAK/STAT signaling pathway in an in vivo model. The efficacy of the dexmedetomidine for IRI in diabetic patient is not resarched yet. The purpose of this experimental study was to evaluate the biochemical and histological effects of dexmedetomidine on hepatic IRI in diabetic rat’s hepatic and renal tissue. METHODOLOGY Animals and Experimental Protocol: This study was conducted in the Physiology Laboratory of Kirikkale University upon the consent of the Experimental Animals Ethics Committee of Kirikkale University. All of the procedures were performed according to the accepted standards of the Guide for the Care and Use of Laboratory Animals. In the study, 28 male Wistar Albino rats, weighing between 250 and 300 g, raised under the same environmental conditions, were used. The rats were kept under 20-21 oC at cycles of 12-hour daylight and 12-hour darkness and had free access to food until 2 hours before the anesthesia procedure. The animals were randomly separated into four groups, each containing 7 rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (Sigma Chemical, St. Louis, MO, USA) at a dose of 65 mg/kg body weight. The blood glucose levels were measured at 72 hrs following this injection. Rats were classified as diabetic if their fasting blood glucose (FBG) levels exceeded 250 mg/dl, and only animals with FBGs of > 250 mg/dl were included in the diabetic groups (dia­betes only, diabetes plus ischemia-reperfusion and diabetes plus dexmedetomidine-ischemia-reperfusion). The rats were kept alive 4 weeks after streptozotocin injection to allow development of chronic dia­betes before they were exposed to ischemia-reperfusion.(19) The rats were weighed before the study. Rats were anesthetized with intraperitoneal ketamine 100 mg/kg. The chest and abdomen were shaved and each animal was fixed in a supine position on the operating table. The abdomen was cleaned with 1% polyvinyl iodine and when dry, the operating field was covered with a sterile drape and median laparotomy was performed. There were four experimental groups (Group C (sham-control; n = 7), (Group DC (diabetes-sham-control; n = 7), Group DIR (diabetes-ischemia-reperfusion; n = 7), and Group DIRD (diabetes-ischemia-reperfusion-dexmedetomidine; n = 7). Sham operation was performed on the rats in Group C and Group DC. The sham operation consisted of mobilization of the hepatic pedicle only. The rats in this group were sacrificed 90 min after the procedure. Hepatic I/R injury was induced in Groups DIR and DIRD respectively with hepatic pedicle clamping using a vascular clamp as in the previous study of Arslan et al.(17) After an ischemic period of 45 min, the vascular clamp was removed. A reperfusion period was maintained for 45 min. In Group DIRD, dexmedetomidine hydrochloride 100 μg/kg, (Precedex 100 μg/2 ml, Abbott®, Abbott Laboratory, North Chicago, Illinois, USA) was administrated via intraperitoneal route 30 minutes before surgery. All the rats were given ketamine 100 mg/kg intraperitoneally and intracardiac blood samples were obtained. Preserving the tissue integrity by avoiding trauma, liver and renal biopsy samples were obtained. Biochemical Analysis: The liver and renal tissues were first washed with cold deionized water to discard blood contamination and then homogenized in a homogenizer. Measurements on cell contest require an initial preparation of the tissues. The preparation procedure may involve grinding of the tissue in a ground glass tissue blender using a rotor driven by a simple electric motor. The homogenizer as a tissue blender similar to the typical kitchen blender is used to emulsify and pulverize the tissue (Heidolph Instruments GMBH & CO KGDiax 900 Germany®) at 1000 U for about 3 min. After centrifugation at 10,000 g for about 60 min, the upper clear layer was taken. MDA levels were determined using the method of Van Ye et al,(20) based on the reaction of MDA with thiobarbituric acid (TBA). In the TBA test reaction, MDA and TBA react in acid pH to form a pink pigment with an absorption maximum at 532 nm. Arbitrary values obtained were compared with a series of standard solutions (1,1,3,3-tetraethoxypropane). Results were expressed as nmol/mg.protein. Part of the homogenate was extracted in ethanol/chloroform mixture (5/3 v/v) to discard the lipid fraction, which caused interferences in the activity measurements of T-SOD, CAT and GST activities. After centrifugation at 10.000 x g for 60 min, the upper clear layer was removed and used for the T-SOD, CAT, GST enzyme activity measurement by methods as described by Durak et al21, Aebi22 and Habig et al23 respectively. One unit of SOD activity was defined as the enzyme protein amount causing 50% inhibition in NBTH2 reduction rate and result were expressed in U/mg protein. The CAT activity method is based on the measurement of absorbance decrease due to H2O2 consumption at 240 nm. The GST activity method is based on the measurement of absorbance changes at 340 nm due to formation of GSH-CDNB complex. Histological determinations: Semiquantitative evaluation technique used by Abdel-Wahhab et al(24) was applied for interpreting the structural changes investigated in hepatic tissues of control and research groups. According to this, (-) (negative point) represents no structural change, while (+) (one positive point) represents mild, (++) (two positive points) medium and (+++) (three positive points) represents severe structural changes. Statistical analysis: The Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA) 20.0 softwre was used for the statistical analysis. Variations in oxidative state parameters, and histopathological examination between study groups were assessed using the Kruskal-Wallis test. The Bonferroni-adjusted Mann-Whitney U-test was used after significant Kruskal-Wallis to determine which groups differed from the others. Results were expressed as mean ± standard deviation (Mean ± SD). Statistical significance was set at a p value < 0.05 for all analyses. RESULTS There was statistically significant difference observed between the groups with respect to findings from the histological changes in the rat liver tissue (hepatocyte degeneration, sinüsoidal dilatation, pycnotic nucleus, prenecrotic cell) determined by light microscopy according to semiquantitative evaluation techniques (p < 0.0001). In Group DIR, hepatocyte degeneration was significantly high compared to Group C, Group DC and Group DIRD (p < 0.0001, p < 0.0001, p = 0.002, respectively), (Table 1, Figure 1-4). Similarly, sinüsoidal dilatation was significantly higher in Group DIR (p < 0.0001, p = 0.004, p = 0.015, respectively). Although, pcynotic nucleus was decreased in Group DIRD, it did not make a significant difference in comparison to Group DIR (p = 0.053), (Table 1, Figure 1-4). The prenecrotic cells were significantly increased in Group DIR, with respect to Group C, Group DC and Group DIRD (p < 0.0001, p = 0.004, p < 0.0001, respectively), (Table 1, Figure 1-4). Table 1. The comparison of histological changes in rat hepatic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR Figure 1: Light microscopic view of hepatic tissue of Group C (control). VC: vena centralis, *: sinusoids. ®: hepatocytes, k: Kupffer cells, G: glycogen granules, mc: minimal cellular changes, Hematoxilen & Eosin x 40 Figure 2: Light-microscopic view of hepatic tissue of Group DC (diabetes mellitus control) (G: Glycogen granules increased in number, (VC: vena centralis, *:sinusoids. ®:hepatocytes, k:Kupffer cells, G: glycogen granules, mc: minimal cellular changes; Hematoxylin & Eosin x 40) Figure 3: Light-microscopic view of hepatic tissue of Group DIR (Diabetes Mellitus and ischemia-reperfusion) (VC: vena centralis, (H) degenerative and hydrophic hepatocytes, (dej) vena centralis degeneration (centrolobar injury) (*): sinusoid dilatation. (←) pycnotic and hyperchromatic nuclei, MNL: mononuclear cell infiltration, (¯) congestion, K: Kupffer cell hyperplasia, (­) vacuolar degeneration (Hematoxylin & Eosin x 40) Figure 4: Light-microscopic view of hepatic tissue of Group DIRD (Diabetes Mellitus and ischemia-reperfusion together with dexmedetomidine applied group) (VC: vena centralis, (MNL) mononuclear cell infiltration, (dej) hydrophilic degeneration in hepatocytes around vena centralis, (conj) congestion, G: glycogen granules, (←) pycnotic and hyperchromatic nuclei, sinusoid dilatation (*) (Hematoxylin & Eosin x 40) Besides, in liver tissue parenchyma, MN cellular infiltration was a light microscopic finding; and showed significant changes among the groups (p < 0.0001). This was significantly higher in Group DIR, compared to Group C, DC, and DIRD (p < 0.0001, p=0.007, p = 0.007, respectively), (Table 1, Figure 1-4). The enzymatic activity of MDA, SOD and GST in hepatic tissues showed significant differences among the groups [(p = 0.019), (p = 0.034). (p = 0.008) respectively]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p = 0.011, p = 0.016, respectively), (Table 2). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.010, p = 0.038, respectively), (Table 2). The GST enzyme activity was significantly higher in Group DIR, when compared to Group C, DC and DIRD (p = 0.007, p = 0.038, p = 0.039, respectively), (Table 2). Table 2. Oxidative state parameters in rat hepatic tissue [Mean ± SD] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR The enzymatic activity of MDA, SOD in renal tissues, showed significant differences among the groups [(p < 0.0001), (p = 0.008) respectively ]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p < 0.0001, p < 0.0001, respectively). Also MDA enzyme activity level was significantly increased in Group DC, in comparison to Group C and Group DIRD (p = 0.003, p = 0.001, respectively), (Table 3). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.032, p = 0.013, respectively), (Table 3). The GST enzyme activity was significantly higher in Group DIR than the other three groups, however; CAT levels were similar among the groups (Table 3). Table 3: Oxidative state parameters in rat nephrotic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR DISCUSSION In this study, we have reported the protective effect of dexmedetomidine in experimental hepatic and renal IRI model in the rat by investigating the MDA and SOD levels biochemically. Besides, hepatic histopathological findings also supported our report. Ischemic damage may occur with trauma, hemorrhagic shock, and some surgical interventions, mainly hepatic and renal resections. Reperfusion following ischemia results in even more injury than ischemia itself. IRI is an inflammatory response accompanied by free radical formation, leucocyte migration and activation, sinusoidal endothelial cellular damage, deteoriated microcirculation and coagulation and complement system activation.1 We also detected injury in hepatic and renal tissue caused by reperfusion following ischemia in liver. Experimental and clinical evidence indicates that OS is involved in both the pathogenesis and the complications of diabetes mellitus.25,26 Diabetes mellitus is a serious risk factor for the development of renal and cardiovascular disease. It is also related to fatty changes in the liver.27 Diabetes-related organ damage seems to be the result of multiple mechanisms. Diabetes has been associated with increased free radical reactions and oxidant tissue damage in STZ-induced diabetic rats and also in patients.26Oxidative stress has been implicated in the destruction of pancreatic β-cells28 and could largely contribute to the oxidant tissue damage associated with chronic hyperglycemia.29 A number of reports have shown that antioxidants can attenuate the complications of diabetes in patients30 and in experimental models.28,31 This study demonstrated that diabetes causes a tendency to increase the IRI. There is a lot of investigations related to the pharmacological agents or food supplements applied for decreasing OS and IRI. Antioxidant agents paly an important role in IRI by effecting antioxidant system or lessening the formation of ROS. It has been reported that anesthetic agents too, are effective in oxidative stress.1 During surgical interventions, it seems rational to get benefit from anesthetic agents in prevention of OS caused by IRI instead of using other agents. It has been declared that; dexmedetomidine; as an α-2 agonist with sedative, hypnotic properties; is important in prevention of renal, focal, cerebral, cardiac, testicular and tourniquet-induced IRI.13-18 On the other hand Bostankolu et al. concluded that dexmedetomidine did not have an additional protective role for tournique induced IRI during routine general anesthesia.32 In this study; we have shown that dexmedetomidine has a reducing effect in IRI in diabetic rats. Some biochemical tests and histopathological evaluations are applied for bringing up oxidative stress and IRI in the tissues. Reactive oxygen species (ROS) that appear with reperfusion injury damage cellular structures through the process of the lipid peroxidation of cellular membranes and yield toxic metabolites such as MDA.33 As an important intermidiate product in lipid peroxidation, MDA is used as a sensitive marker of IRI.34 ROS-induced tissue injury is triggered by various defense mechanisms.35 The first defence mechanisms include the antioxidant enzymes of SOD, CAT, and GPx. These endogenous antioxidants are the first lines of defence against oxidative stres and act by scavenging potentially damaging free radical moieties.36 There is a balance between ROS and the scavenging capacity of antioxidant enzymes.1-8 In this study, for evaluation of oxidative damage and antioxidant activity, MDS, SOD, GST and CAT levels were determined in liver and kidney tissues. MDA levels in hepatic and renal tissues were higher in Group DIR compared to Group C and Group DIRD. GST levels were higher in Group DIR compared to all the other three groups. When the groups were arranged from highest to lowest order, with respect to CAT levels, the order was; Group DIR, Group DIRD, Group DC and Group C. However, the difference was not significant. The acute phase reactant MDA, as a marker of OS, was found to be high in Group DIR and low in Group DIRD. This could be interpreted as the presence of protective effect of dexmedetomidine in IRI. IRI developing in splanchnic area causes injury also in the other organs.35 Leithead et al showed that clinically significant hepatic IRI demonstrates a strong relationship with peri-operative acute kidney injury.2 In our experimental research that showed correlation to that of research by Leithead et al. After hepatic IRI in diabetic rats renal OS marker MDA levels were significantly more in Group DIR than Group DIRD. In our study, we observed histopathological changes in the ischemic liver tissue and alterations in the level of MDA, SOD, GST and CAT levels which are OS markers. Histopathological changes of the liver tissues are hepatocyt degeneration, sinusoidal dilatation, nuclear picnosis, celluler necrosis, mononuclear cell infiltrationat paranchimal tissue. These histopathological injury scores were significantly lower in the Group DIRD than those in group DIR. LIMITATION Study limitation is there was no negative control group, as this type of surgical intervention is not possible in rats without anesthesia. CONCLUSION The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease ischemia-reperfusion injury. Conflict of interest and funding: The authors have not received any funding or benefits from industry or elsewhere to conduct this study. 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