Journal articles on the topic '209999 Other health not elsewhere classified'

Due to the high levels of alcohol use, alcohol-attributable mortality and burden of disease, and detrimental drinking patterns, Lithuania implemented a series of alcohol control policies within a relatively short period of time, between 2008 and 2019. Based on their expected impact on alcohol consumption and alcohol-attributable harm, as well as their target population, these policies have been classified using a set of objective criteria and expert opinion. The classification criteria included: positive vs. negative outcomes, mainly immediate vs. delayed outcomes, and general population vs. specific group outcomes. The judgement of the alcohol policy experts converged on the objective criteria, and, as a result, two tiers of intervention were identified: Tier 1—highly effective general population interventions with an anticipated immediate impact; Tier 2—other interventions aimed at the general population. In addition, interventions directed at specific populations were identified. This adaptable methodological approach to alcohol control policy classification is intended to provide guidance and support for the evaluation of alcohol policies elsewhere, to lay the foundation for the critical assessment of the policies to improve health and increase life expectancy, and to reduce crime and violence.

AbstractObjectivesTo estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish.DesignCross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance.SettingBaseline examinations conducted in 1991–1994 in Malmö, Sweden.SubjectsA sub-sample of 8599 women and 6575 men of the MDC cohort.ResultsThe mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (κ = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake.ConclusionsThe estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

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.

AbstractObjective:To determine whether volumetric measures of the hippocampus, entorhinal cortex, and other cortical measures can differentiate between cognitively normal individuals and subjects with mild cognitive impairment (MCI).Method:Magnetic resonance imaging (MRI) data from 46 cognitively normal subjects and 50 subjects with MCI as part of the Boston University Alzheimer’s Disease Center research registry and the Alzheimer’s Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical, subcortical, and hippocampal subfield volumes were generated from each subject’s MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to identify subjects as control or MCI.Results:A model containing regions of interest (superior temporal cortex, caudal anterior cingulate, pars opercularis, subiculum, precentral cortex, caudal middle frontal cortex, rostral middle frontal cortex, pars orbitalis, middle temporal cortex, insula, banks of the superior temporal sulcus, parasubiculum, paracentral lobule) fit the data best (R2= .7310, whole model test chi-square = 97.16,p< .0001).Conclusions:MRI data correctly classified most subjects using measures of selected medial temporal lobe structures in combination with those from other cortical areas, yielding an overall classification accuracy of 93.75%. These findings support the notion that, while volumes of medial temporal lobe regions differ between cognitively normal and MCI subjects, differences that can be used to distinguish between these two populations are present elsewhere in the brain.

Purpose: To analyze 10-year trends in utilization of visual field tests for adult glaucoma or glaucoma-suspect patients using the Korean Health Insurance Review and Assessment data.Methods: Health claims for the years 2010 to 2019, as recorded via Korea’s Health Insurance Review and Assessment service, were accessed. We identified glaucoma patients using the glaucoma diagnostic codes H40 (glaucoma) and H42 (glaucoma in other diseases classified elsewhere). For verification of the glaucoma diagnosis, information on any antiglaucoma medication prescriptions and ocular surgery history also was obtained. Visual field testing data was isolated using procedural codes E6690 (kinetic perimetry) and E6691 (standard automated perimetry [SAP]) performed in tertiary hospitals. Any changes in visual field test utilization were identified using regression trend analysis.Results: From 2010 to 2019, the total number of SAP procedures performed in tertiary hospitals for either glaucoma or glaucoma-suspect patients increased gradually from 93,459 to 216,433. With regard to kinetic perimetry examinations, the total number decreased gradually from 6,364 to 3,792. The yearly average SAP number per patient showed a slight increase, from 1.168 to 1.248 (ß = 0.008, R2 = 0.669, p = 0.004). Meanwhile, the yearly average number of kinetic perimeter examinations per patient showed a significant decrease, from 1.093 to 0.940 (ß = -0.013, R2 = 0.580, p = 0.010).Conclusions: Between 2010 and 2019, the yearly average number of SAP procedures performed per glaucoma or glaucoma-suspect patient increased in Korea. Meanwhile, the yearly average number of kinetic perimetry examinations per patient significantly decreased.

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare form of astrocytic neoplasm most commonly found in children and young adults. This neoplasm, which is classified as a Grade II tumor by the World Health Organization classification of tumors of the central nervous system, carries a relatively favorable outcome. It is usually found supratentorially in cortical regions of the cerebral hemispheres, and as such, presenting symptoms are similar to other supratentorial cortical neoplasms; with seizures being a common initial symptom. Due to the rarity of this type of neoplasm, PXA arising elsewhere in the brain is often not included in the initial differential diagnosis. Case Description: This report presents an extremely rare patient with PXA arising in the suprasellar region who presented with progressive peripheral vision loss. Magnetic resonance imaging of the brain demonstrated a heterogeneous suprasellar mass with cystic and enhancing components initially; the most likely differential diagnosis was craniopharyngioma. The patient underwent endoscopic endonasal resection of the tumor. Microscopically, the tumor was consistent with a glial neoplasm with variable morphology. Based on these findings along with further immunohistochemical workup, the patient was diagnosed with a PXA arising in the suprasellar region. At the 1-year follow-up, the patient remained free of recurrence. Although rare PXA originating in other uncommon locations, such as the spinal cord, cerebellum, the ventricular system, and the pineal region have been previously described. Conclusion: Although rare, PXA should be included in the differential diagnosis for solid-cystic tumors arising in the suprasellar region in young adults.

Purpose The purpose of this paper is to gather epidemiologicalinformation concerning firesetters with intellectual disabilities (ID) in Denmark to identify the assessment and treatment needs of this population and inform further research in this area. Design/methodology/approach The records held by the Danish Ministry of Justice concerning all firesetters with ID convicted of deliberate firesetting were reviewed for the period January 2001 to December 2010 inclusive. File information was extracted for 83 offenders concerning: demographic and personal characteristics; mental health characteristics; offending behaviour; offence-specific factors; and motives for offending. A sub-group of seven offenders were interviewed to explore some of the themes that emerged from the file review. Findings The majority of study participants were male and were classified as having mild ID and around 50 per cent had additional mental health problems. Many came from disturbed and deprived backgrounds. Two-thirds had set more than one fire and over 60 per cent had convictions for offences other than firesetting. Alcohol was involved in the firesetting behaviour in a significant proportion of cases (25 per cent). The motives for setting fires were – in descending order – communication (of anger, frustration and distress), fire fascination and vandalism. Interviews with participants indicated the important communicative function of firesetting, the difficulties people had in talking about and acknowledging their firesetting behaviour, and lack of access to targeted interventions. Research limitations/implications Interventions for Danish firesetters with ID, as for firesetters with ID elsewhere, need to target the communicative function of this behaviour, along with offenders’ lack of insight and initial reluctance to accept responsibility for their behaviour and associated risks. Adjunctive treatment is required to address the psychiatric comorbidity experienced by many of these offenders, along with the alcohol use/misuse that is associated with many of these offences. Originality/value This is the first study concerning nature and needs of firesetters with ID in Denmark.

Background: Adverse drug reactions (ADRs) constitute a major clinical problem in terms of human suffering and increased health care costs. To study the adverse drug reactions reported in a tertiary care hospital and study of causality assessment and severity of adverse drug reaction (ADR) cases reported.Methods: A prospective observational study was conducted as part of pharmacovigilance program over 12months between September 2015 and August 2016. Adverse drug reactions reported from hospital were filled into Suspected ADR - CDSCO forms and submitted to pharmacovigilance unit. Causal relationship was assessed and categorized by Naranjo’s algorithm and WHO - UMC causality scale. The severity of each ADR was assessed using Modified Hartwig and Siegel scale.Results: Total 120 cases were reported over 12 months. Among them, 66% were in males and 55% were in females. The majority of ADRs were due to antimicrobial agents (40.78%) followed by haematinics (12%) and anti-epileptics (10%). Maximum number of patients (30.25%) reported with dermatological manifestations. Highest number of ADRs was reported from the department of medicine (45%). As per Naranjo’s scale, 54% reports were assessed as probable and 46% classified as possible. Majority of cases were mild to moderate in severity.Conclusions: The pattern of ADRs reported in our hospital is similar with the pattern of studies conducted in other hospitals elsewhere. This study provides a database of ADRs due to commonly used drugs in our hospital, which will help clinicians for their optimum and safe use. Hence effective pharmacovigilance is required for the use of these drugs and their safety assessment.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular.

Abstract The World Health Organization (WHO) central nervous system (CNS) tumor classification has represented the primary source of diagnosis and grading criteria of brain tumors. Nonetheless, recent advances of studies on their molecular alterations require more rapid update of recommendations for clinical practice. To accomplish this, cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established in 2016 and has published four updates. For adult gliomas, update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed a new term NEC (Not Elsewhere Classified); update 2 revised clarifications regarding diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant; update 3 proposed molecular criteria for an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma, which would behave similarly to a grade IV glioblastoma. Nonetheless, no consensus on pathologic or molecular markers that could be incorporated into a more clinically relevant grading scheme for IDH-mutant gliomas has been reached. The molecular alterations previously studied using relatively large cohorts include CDKN2A/B homozygous deletion, CDK4 amplification, RB1 mutation/homozygous deletion, PIK3CA or PIK3R1 mutations, PDGFRA amplification, NMYC amplification, global hypomethylation, genomic instability and chromosome 14 loss. The proliferative activity, based on the mitotic count or Ki67 indices, and other morphologic features typical of a high grade that might stratify the risk better than the current criteria have also been evaluated. Despite the discordance among the results of previous studies, CDKN2A/2B homozygous deletions have been shown prognostic significance in high-grade IDH-mutant astrocytomas and microvascular proliferation stratifies IDH-mutant gliomas lacking a CDKN2A homozygous deletion, suggesting that the integration of molecular information and traditional histological findings is still essential for achieving maximum risk stratification of adult cases of IDH-mutant diffuse gliomas. The grading scheme for adult IDH-mutant as well as wild-type gliomas should therefore be revised in the next WHO update.

<p class="abstract"><strong><span lang="EN-US">Background: </span></strong>Reliable data on mortality and morbidity among women of reproductive age are scarce in India. The present study is the Rajasthan component of a large multi-centric study on cause of death by verbal autopsy conducted in five states of India. The data pertaining to deaths among women of reproductive age are presented. </p><p class="abstract"><strong><span lang="EN-US">Methods: </span></strong>House-to-house surveys of a representative population from rural and urban areas in six districts of Rajasthan were undertaken by Probability of Proportion to Size (PPS) sampling. Information on death was obtained from the relatives of the deceased and cause of death was assigned using the standardized algorithm prepared for the purpose. International Classification of Diseases - ICD-10 was used to code the assigned cause of death. </p><p class="abstract"><strong><span lang="EN-US">Results: </span></strong>A total of 231 deaths of women of reproductive age were investigated, of which 36 (16%) were maternal deaths while 195 (84%) were non-maternal deaths. Nine out of ten maternal deaths were in rural area.</p><p class="abstract"><strong><span lang="EN-US">Conclusions: </span></strong>Certain infectious and parasitic diseases; pregnancy, childbirth and the puerpurium; injury, poisoning and other consequences of external causes; and symptoms, signs and abnormal clinical and laboratory findings not elsewhere classified were found to be the major killers among the women of reproductive age. A comprehensive approach that includes in addition to reproductive health interventions, interventions addressing underlying illiteracy among women and social reforms needs to be undertaken. </p><p class="keywords"><strong><span lang="EN-US">Keywords: </span></strong>Maternal deaths, Non-maternal deaths, Women of reproductive age, Verbal autopsy</p>

Background: The NHSN parameter estimate for predicted number of central-line–associated bloodstream infection (CLABSI) is the same for gastroenterology wards as other specialty wards, such as behavioral health and gerontology. We conducted this study to contribute to the body of knowledge surrounding the risk for hospital-acquired bloodstream infection (HABSI) in patients with and without hepatic failure. The Cleveland Clinic is a 1,200-bed, multispecialty hospital with a solid-organ transplant service. Patients with hepatic failure who do not require critical care are housed on 36-bed unit A. On unit A, 43% of patients are under hepatology or gastroenterology service, although 51% of patients are under general internal medicine. Overall, unit A has a high incidence of HABSI. Methods: Surveillance for HABSI and CLABSI is performed at the Cleveland Clinic per NHSN protocol. All patients with a midnight stay on unit A from January 2019 through September 2021 were dichotomized as having hepatic failure (yes or no) if they ever received the International Classification of Diseases Tenth Revision code for “hepatic failure, not elsewhere classified.” We joined the diagnostic code to patient days and central-line-days databases and summarized the data using Microsoft Excel software. We stratified the number of patients, patient days, device days, infection classification, and hospital length of stay by whether the patient had hepatic failure, and we compared the incidence of HABSI and CLABSI between the 2 groups using OpenEpi version 3.01 software. Results: We identified 72 HABSIs among 4,285 patients who stayed on unit A for 30,910 patient days during the study period. The incidences of HABSI in patients with and without hepatic failure were 39.0 and 13.9 per 10,000 patient days, respectively (P < .001). The incidence of CLABSI was 5.4 and 1.9 per 1,000 line days, respectively (P = .01). Patients with hepatic failure stayed longer (11.5 vs 5.9 days), yet the central-line utilization ratios were not substantially different (0.25 vs 0.24). Enterococcus was the most common pathogen involved in CLABSI in both groups (Table 2). Conclusions: Patients with hepatic failure experienced CLABSI more frequently than patients without hepatic failure, stayed longer in the hospital, and were less likely have HABSI attributed to another primary focus of infection according to NHSN definitions. Although hepatic failure may be among the most severe conditions among patients in a gastroenterology ward, we have demonstrated that these units house a population uniquely susceptible to HABSI and CLABSI.Funding: NoneDisclosures: None

Abstract Background Patients with solid tumors treated at a National Cancer Institute designated cancer center (NCI-CC) have been found to have improved survival when compared to those treated elsewhere. Few population-based studies have evaluated the association between location of care, complications associated with intensive therapy and early mortality (defined here as death ² 60 days from diagnosis) in patients with AML. Methods Using linked data from the California Cancer Registry and Patient Discharge Dataset from 1999 to 2012, we identified patients ³15 years of age diagnosed with AML who received inpatient treatment. Hospitals where patients received their care were classified as either NCI-CC or non-NCI designated facilities (non-NCI-CC). Logistic regression was used to estimate associations between patient characteristics (age, sex, race/ethnicity, year of diagnosis, marital status, neighborhood socioeconomic status, health insurance, and medical comorbidities) and location of care (NCI-CC vs non-NCI-CC facilities), and then to build a propensity score. Inverse probability weighted logistic regression models were used to determine associations between location of care and complications with early mortality. Interactions of complications and location of care with early mortality were also considered. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results Of the 5613 patients with AML identified, 1406 (25%) were treated at an NCI-CC. Compared to patients treated elsewhere, AML patients treated at an NCI-CC were more likely to be <65 years of age, Hispanic (versus non-Hispanic white), live in higher socioeconomic status neighborhoods, have fewer comorbidities and have Medicare or public (versus private) health insurance. Patients treated at NCI-CCs had higher rates of renal failure (21% vs 18%, P=0.03) and lower rates of respiratory failure (11% vs 14%, P=0.002) and sepsis (33% vs 36%, P=0.04) than those treated at non-NCI-CCs. Rates of bleeding, thrombosis, liver failure and cardiac arrest did not differ by location of care. After propensity-score weighting, baseline characteristics were balanced between patients treated at NCI-CCs versus non-NCI-CCs (all standardized mean differences <2.3%). In multivariable, inverse probability weighted models, treatment at an NCI-CC (versus non-NCI-CC) was associated with lower early mortality (OR 0.50, CI 0.42-0.59) (Table). Complications associated with higher early mortality, regardless of treatment location, included: bleeding (OR 1.91, CI 1.54-2.37), liver (OR 3.41, CI 1.91-6.09), renal (OR 2.39, CI 1.97-2.90) and respiratory (OR 6.08, CI 4.88-7.57) failure and cardiac arrest (OR 15.28, CI 8.11-27.78) (Table). The impact of complications on early mortality did not differ by location of care with the exception of respiratory failure (P for interaction=0.001); AML patients with respiratory failure had a higher odds of early mortality when treated at non-NCI-CCs (OR 8.59, CI 6.66-11.07) versus NCI-CCs (OR 4.43, CI 2.68-7.33). Other factors significantly associated with early mortality included younger age, treatment after 2002, non-Hispanic White race/ethnicity (versus African Americans, Hispanics and Asians), single marital status (versus married), residence in low socioeconomic status neighborhoods (versus high) and presence of any comorbidities (versus none). Conclusions In patients with AML, initial treatment at a NCI-CC is associated with 50% reduction in early mortality than treatment at a non-NCI-CC, adjusted for baseline socio-demographic variables, comorbidities and complications within 60 days. Lower early mortality may result from differences in supportive care practices, hospital or provider experience and access to clinical trials at NCI-CCs. Future studies should evaluate the specific differences in care at NCI-CCs to inform strategies to improve early mortality outcomes for all AML patients. Table. Table. Disclosures No relevant conflicts of interest to declare.

Background Long-term PI-based treatment is associated with improved outcomes in MM. Nonetheless, prolonged therapy with parenteral PIs (e.g. bortezomib) can be challenging in the real world, with median duration of therapy (DOT) of 4-7 months. Barriers to this long-term approach may include the burden of repeated intravenous/subcutaneous administration, difficulty travelling to/accessing treatment centers (e.g. due to environmental factors, travel restrictions, social/family situations), patient preference for treatment outside of a hospital or clinic setting, comorbidities, and toxicity. The US MM-6 study (NCT03173092) is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral ixazomib-based therapy (ixazomib-lenalidomide-dexamethasone; IRd) in the diverse US community population with the aim of increasing PI-based treatment duration while maintaining quality of life and improving outcomes. We report updated efficacy and safety for the first 101 patients. Methods Transplant-ineligible/delayed-transplant (&gt;24 months) NDMM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at US community sites (including Veterans Affairs hospitals) to receive IRd (ixazomib 4 mg, days 1, 8, 15; lenalidomide 25 mg, days 1-21; dexamethasone 40 mg, days 1, 8, 15, 22) for up to 39 x 28-day cycles or until progression/toxicity. The primary endpoint is progression-free survival (PFS); key secondary endpoints include rates of partial (PR), very good PR (VGPR), and complete response (CR), and DOT. Results As of June 1 2020, 101 patients had been treated at 21 sites. Median age was 73 years (range 48-90), with 46% aged ≥75 years; 16% and 10% were of African American and Hispanic ethnicity, respectively. Table 1 summarizes the key characteristics of these real-world patients. A total of 95% of patients had ≥1 comorbidity at the start of IRd therapy including renal and urinary disorders (38%), cardiac disorders (29%), peripheral neuropathy (PN; 14%), and diabetes mellitus (13%) (Table 2). With 53 (52%) patients remaining on therapy and enrollment ongoing, mean duration of PI therapy from the start of bortezomib-based induction was 12.4 months, and mean duration of IRd therapy after iCT was 9.2 months (Table 3). Patients have received up to 29.4 months (31 cycles) of IRd to date. The overall response rate (ORR) after bortezomib-based induction was 62% (7% CR, 32% ≥VGPR). After iCT to IRd, the ORR increased to 71%, with the CR and ≥VGPR rates increasing to 29% and 53%, respectively (Figure); of 33 patients with stable disease following bortezomib-based induction, 14 (42%) achieved CR (n=10) or VGPR (n=4) after iCT. With a median follow-up of 12 months and enrollment ongoing, 13 patients had progressed and two had died during PFS analysis. The 12-month PFS rate was 84% (95% CI, 73-91) from the start of bortezomib-based induction and 80% (95% CI, 69-88) from the start of IRd. During IRd treatment to date, 91% of patients have had treatment-emergent adverse events (TEAEs) (54% grade ≥3). Grade 3 TEAEs (≥5% of patients) were diarrhea (8%), pneumonia (7%), and syncope (5%). TEAEs led to study drug modification in 52% of patients and discontinuation in 7% of patients; 37% had serious TEAEs. Diarrhea, nausea, and vomiting occurred in 43%, 23%, and 14% of patients (8%, 2%, 2% grade 3), and led to dose modification in 11%, 5%, and 2%. PN (not elsewhere classified; high-level term) occurred in 32% of patients (2% grade 3) and led to dose modification in 9%. There were three on-study deaths (i.e. occurring &lt;30 days after last dose). Conclusions US MM-6 patients reflect the heterogeneous real-world US MM population; the population for this study includes patients from the community who may not be eligible for traditional clinical trials. These updated data in mostly elderly, comorbid, NDMM patients treated in the community setting demonstrate the feasibility and tolerability of iCT to IRd after 3 cycles of bortezomib-based induction; approximately half of patients remain on treatment, and enrollment is ongoing. iCT to IRd resulted in improved responses, with increased rates of ≥VGPR, and prolonged DOT and may thereby improve outcomes for real-world patients. iCT to an all oral regimen could also prevent treatment interruptions for patients who are unable to or prefer not to travel in the context of travel restrictions or other factors. Disclosures Girnius: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yimer:TG Therapeutics: Consultancy; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Sanofi: Speakers Bureau; Texas Oncology: Current Employment; BeiGene: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Celgene, a Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Karyopharm: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Epizyme: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months. Noga:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Manda:AbbVie: Other: Investigator in AbbVie-sponsored clinical trials. Lyons:Texas Oncology/US Oncology: Current Employment; Novartis: Honoraria. Bogard:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Whidden:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Cherepanov:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Lu:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Aiello:Takeda: Honoraria; Travera: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria. Richter:Celgene: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Speakers Bureau; Janssen: Speakers Bureau; Sanofi: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy; Secura Bio: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Antengene: Consultancy. Rifkin:McKesson: Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other: Stock ownership; Takeda, Amgen, Celgene, BMS, Mylan, Coherus BioSciences, Fresenius: Consultancy; AbbVie: Other: Investigator in AbbVie sponsored clinical trials; Takeda, Amgen, BMS (Celgene): Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Real-world evaluation of long-term proteasome inhibition with ixazomib in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma in non-transplant patients with stable disease after 3 cycles of a bortezomib-based induction.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular. Outbreaks, defined as excess cases of a particular disease or illness which outweighs the response capabilities, have the capacity to overwhelm health care facilities and need timely response and attention to details in order to avoid potentially disastrous sequelae . In this day and age when improvement in public health practices have significantly curtailed outbreak of various diseases, certain viral illnesses continue to make headlines. One of the notable vector borne infectious disease affecting significant portions of south east Asia in the early part of twenty first century is 'Dengue fever'. Dreaded as it is by those suffering from the illness, a lot of the hysteria created is secondary to a lack of education and understanding of the nature of the disease and at times a result of disinformation campaign for vested interests by certain political and media sections.'Dengue' in fact is a Spanish word, assumed to have originated from the Swahili phrase -ka dinga peppo -which describes the disease as being caused by evil spirit. 1 Over the course of time it has been called 'breakbone fever', 'bilious vomiting fever', 'break heart fever', 'dandy fever', 'la dengue' and 'Phillipine, Thai and Singapore hemorrhagic fever' Whilst the first reported case referring to dengue fever as a water poison spread by flying insects, exists in the Chinese medical encyclopedia from Jin Dynasty (265-420 AD), the disease is believed to have disseminated from Africa with the spread of the primary vector, aedes egypti, in the 15th to 19th century as a result of globalisation of slave trade 45In 80% of the patients affected by this condition the presentation is rather insidious and at best characterized by mild fever. The classical 'Dengue fever' present in about 5% of the cases is characterized by high temperature, body aches, vomiting and at times a skin rash. The disease may regresses in two to seven days. However inrare instances (<5%) it may develop into more serious conditions such as Dengue hemorrhagic fever whereby the platelet count is significantly reduced leading to bleeding tendencies and may even culminate in a more life threatening presentation i.e Dengue shock syndrome.6To understand the actual dynamics of Dengue epidemic it is important to understand the mode of its spread in affected areas. Aedes mosquito (significantly Aedes Egypti) acts a vector for this disease. Early morning and evening times7 are favoured by these mosquitos to feed on their prey. There is some evidence that the disease may be transmitted via blood products and organ donation. 8 Moreover vertical transmission (mother to child) has also been reported 9Diagnostic investigations include blood antigen detection through NS-I or nucleic acid detection via PCR. IO Cell cultures and specific serology may also be used for confirming the underlying disease. Whilst sporadic and endemic cases are part of routine medical practice and may not raise any alarm bells, outbreaks certainly need mobilization of appropriate resources for effective control. Needless to say 'prevention is better than cure' and should be the primary target of the health authorities in devising strategies for disease control.The WHO recommended 'Integrated Vector control programme', lays stress on social mobilisation and strengthening of public health bodies, coherent response of health and related departments and effective capacity building of relevant personnel and organisations as well as the community at risk. For Aedes Egypti the primary control revolves around eliminating its habitats such as open sources of water. In a local perspective in our city Peshawar, venue of the recent dengue epidemic, it may be seen in the form of incidental reservoirs such as receptacles and tyres dumped in open areas such as roof tops with rain water accumulating in them and provtdjng excellent breeding habitats, Larvicidal and insecticides may be added to more permanent sources such as watertanks and farm lands. There is not much of a role for spraying with organophosphorous agents which is at times resorted to for public consumption. Public education is the key to any effective strategy which must highlight the need for wearing clothing that fully covers the skin, avoiding unnecessary early morning and evening exposure to vector agents, application of insect repellents and use of mosquito nets. It is also important not to panic if affliction with the disease is suspected as in a vast majority of instances it is a self limiting illness without any long term harmful effects and needs simple conservative management like antipyretics and analgesics.An important consideration for responsible authorities in a dengue epidemic is to ensure that maximum management facilities for simple cases are provided at the community level through primary and secondary health care facilities and that the tertiary care hospitals are not inundated with all sort of patients demanding consultation. These later facilities should be reserved for those patients who end up with any complications or more severe manifestation of the disease.Research is underway to develop an ideal vaccine for Dengue fever. In 2016, a vaccine by the name 'Dengvaxia' was marketed in Phillipines and Indonesia. However with development of new serotypes of the virus, its efficacy has been somewhat compromised.As for treatment , there are no specific antiviral drugs. Management is symptomatic revolving mainly around oral and intravenous hydration. Paracetamol (Acetaminophen) is used for fever as compared to NSAIDS such as Ibuprophen infusion as well as blood and platelet transfusion.Data to date shows that slightly more than twenty three thousand people have been diagnosed with dengue over the past three months ie August to October there is a lower risk of bleeding with the former. Those with more severe form of the disease may need Dextran 2017, in Peshawar, Pakistan with around fourteen thousand needing admission and about sixty nine recorded deaths. The mortality is well within the acceptable international standards of less than 1% for the disease. In the backdrop of all the debate surrounding the current epidemic, one can infer that such outbreaks are best addressed with effective planningwell ahead of the time before the disease threatens to spiral out of control. Simple measures such as covering water storage facilities, using larvicidals where practical, use of insect repellents, mosquito nets and avoiding unnecessary exposure can offerthe best protection. Public health messages via print and electronic media can help educate people in affected areas and allay any anxiety building up from a fear of developing life threatening complications. Health department must mobilise all its resources to ensure local management of diagnosed patients with simple dengue fever and facilitate hospital admission only for those suffering from more severe form of the disease. Moreover the media hype into such situations needs to be addressed through constant updates and discouraging any negative politicking on the issue. To sum up Dengue fever is not really an affliction to be dreaded provided it is viewed and managed in the right perspective.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular. Outbreaks, defined as excess cases of a particular disease or illness which outweighs the response capabilities, have the capacity to overwhelm health care facilities and need timely response and attention to details in order to avoid potentially disastrous sequelae . In this day and age when improvement in public health practices have significantly curtailed outbreak of various diseases, certain viral illnesses continue to make headlines. One of the notable vector borne infectious disease affecting significant portions of south east Asia in the early part of twenty first century is 'Dengue fever'. Dreaded as it is by those suffering from the illness, a lot of the hysteria created is secondary to a lack of education and understanding of the nature of the disease and at times a result of disinformation campaign for vested interests by certain political and media sections.'Dengue' in fact is a Spanish word, assumed to have originated from the Swahili phrase -ka dinga peppo -which describes the disease as being caused by evil spirit. 1 Over the course of time it has been called 'breakbone fever', 'bilious vomiting fever', 'break heart fever', 'dandy fever', 'la dengue' and 'Phillipine, Thai and Singapore hemorrhagic fever' Whilst the first reported case referring to dengue fever as a water poison spread by flying insects, exists in the Chinese medical encyclopedia from Jin Dynasty (265-420 AD), the disease is believed to have disseminated from Africa with the spread of the primary vector, aedes egypti, in the 15th to 19th century as a result of globalisation of slave trade 45In 80% of the patients affected by this condition the presentation is rather insidious and at best characterized by mild fever. The classical 'Dengue fever' present in about 5% of the cases is characterized by high temperature, body aches, vomiting and at times a skin rash. The disease may regresses in two to seven days. However inrare instances (<5%) it may develop into more serious conditions such as Dengue hemorrhagic fever whereby the platelet count is significantly reduced leading to bleeding tendencies and may even culminate in a more life threatening presentation i.e Dengue shock syndrome.6To understand the actual dynamics of Dengue epidemic it is important to understand the mode of its spread in affected areas. Aedes mosquito (significantly Aedes Egypti) acts a vector for this disease. Early morning and evening times7 are favoured by these mosquitos to feed on their prey. There is some evidence that the disease may be transmitted via blood products and organ donation. 8 Moreover vertical transmission (mother to child) has also been reported 9Diagnostic investigations include blood antigen detection through NS-I or nucleic acid detection via PCR. IO Cell cultures and specific serology may also be used for confirming the underlying disease. Whilst sporadic and endemic cases are part of routine medical practice and may not raise any alarm bells, outbreaks certainly need mobilization of appropriate resources for effective control. Needless to say 'prevention is better than cure' and should be the primary target of the health authorities in devising strategies for disease control.The WHO recommended 'Integrated Vector control programme', lays stress on social mobilisation and strengthening of public health bodies, coherent response of health and related departments and effective capacity building of relevant personnel and organisations as well as the community at risk. For Aedes Egypti the primary control revolves around eliminating its habitats such as open sources of water. In a local perspective in our city Peshawar, venue of the recent dengue epidemic, it may be seen in the form of incidental reservoirs such as receptacles and tyres dumped in open areas such as roof tops with rain water accumulating in them and provtdjng excellent breeding habitats, Larvicidal and insecticides may be added to more permanent sources such as watertanks and farm lands. There is not much of a role for spraying with organophosphorous agents which is at times resorted to for public consumption. Public education is the key to any effective strategy which must highlight the need for wearing clothing that fully covers the skin, avoiding unnecessary early morning and evening exposure to vector agents, application of insect repellents and use of mosquito nets. It is also important not to panic if affliction with the disease is suspected as in a vast majority of instances it is a self limiting illness without any long term harmful effects and needs simple conservative management like antipyretics and analgesics.An important consideration for responsible authorities in a dengue epidemic is to ensure that maximum management facilities for simple cases are provided at the community level through primary and secondary health care facilities and that the tertiary care hospitals are not inundated with all sort of patients demanding consultation. These later facilities should be reserved for those patients who end up with any complications or more severe manifestation of the disease.Research is underway to develop an ideal vaccine for Dengue fever. In 2016, a vaccine by the name 'Dengvaxia' was marketed in Phillipines and Indonesia. However with development of new serotypes of the virus, its efficacy has been somewhat compromised.As for treatment , there are no specific antiviral drugs. Management is symptomatic revolving mainly around oral and intravenous hydration. Paracetamol (Acetaminophen) is used for fever as compared to NSAIDS such as Ibuprophen infusion as well as blood and platelet transfusion.Data to date shows that slightly more than twenty three thousand people have been diagnosed with dengue over the past three months ie August to October there is a lower risk of bleeding with the former. Those with more severe form of the disease may need Dextran 2017, in Peshawar, Pakistan with around fourteen thousand needing admission and about sixty nine recorded deaths. The mortality is well within the acceptable international standards of less than 1% for the disease. In the backdrop of all the debate surrounding the current epidemic, one can infer that such outbreaks are best addressed with effective planningwell ahead of the time before the disease threatens to spiral out of control. Simple measures such as covering water storage facilities, using larvicidals where practical, use of insect repellents, mosquito nets and avoiding unnecessary exposure can offerthe best protection. Public health messages via print and electronic media can help educate people in affected areas and allay any anxiety building up from a fear of developing life threatening complications. Health department must mobilise all its resources to ensure local management of diagnosed patients with simple dengue fever and facilitate hospital admission only for those suffering from more severe form of the disease. Moreover the media hype into such situations needs to be addressed through constant updates and discouraging any negative politicking on the issue. To sum up Dengue fever is not really an affliction to be dreaded provided it is viewed and managed in the right perspective.

Environments containing significant concentration of NaCl such as salt lakes harbor extremophiles microorganisms which have a great biotechnology interest. To explore the diversity of Bacteria in Chott Tinsilt (Algeria), an isolation program was performed. Water samples were collected from the saltern during the pre-salt harvesting phase. This Chott is high in salt (22.47% (w/v). Seven halophiles Bacteria were selected for further characterization. The isolated strains were able to grow optimally in media with 10–25% (w/v) total salts. Molecular identification of the isolates was performed by sequencing the 16S rRNA gene. It showed that these cultured isolates included members belonging to the Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus genera with less than 98% of similarity with their closest phylogenetic relative. The halophilic bacterial isolates were also characterized for the production of biosurfactant and industrially important enzymes. Most isolates produced hydrolases and biosurfactants at high salt concentration. In fact, this is the first report on bacterial strains (A4 and B4) which were a good biosurfactant and coagulase producer at 20% and 25% ((w/v)) NaCl. In addition, the biosurfactant produced by the strain B4 at high salinity (25%) was also stable at high temperature (30-100°C) and high alkalinity (pH 11).Key word: Salt Lake, Bacteria, biosurfactant, Chott, halophiles, hydrolases, 16S rRNAINTRODUCTIONSaline lakes cover approximately 10% of the Earth’s surface area. The microbial populations of many hypersaline environments have already been studied in different geographical regions such as Great Salt Lake (USA), Dead Sea (Israel), Wadi Natrun Lake (Egypt), Lake Magadi (Kenya), Soda Lake (Antarctica) and Big Soda Lake and Mono Lake (California). Hypersaline regions differ from each other in terms of geographical location, salt concentration and chemical composition, which determine the nature of inhabitant microorganisms (Gupta et al., 2015). Then low taxonomic diversity is common to all these saline environments (Oren et al., 1993). Halophiles are found in nearly all major microbial clades, including prokaryotic (Bacteria and Archaea) and eukaryotic forms (DasSarma and Arora, 2001). They are classified as slight halophiles when they grow optimally at 0.2–0.85 M (2–5%) NaCl, as moderate halophiles when they grow at 0.85–3.4 M (5–20%) NaCl, and as extreme halophiles when they grow at 3.4–5.1 M (20–30%) NaCl. Hyper saline environments are inhabited by extremely halophilic and halotolerant microorganisms such as Halobacillus sp, Halobacterium sp., Haloarcula sp., Salinibacter ruber , Haloferax sp and Bacillus spp. (Solomon and Viswalingam, 2013). There is a tremendous demand for halophilic bacteria due to their biotechnological importance as sources of halophilic enzymes. Enzymes derived from halophiles are endowed with unique structural features and catalytic power to sustain the metabolic and physiological processes under high salt conditions. Some of these enzymes have been reported to be active and stable under more than one extreme condition (Karan and Khare, 2010). Applications are being considered in a range of industries such as food processing, washing, biosynthetic processes and environmental bioremediation. Halophilic proteases are widely used in the detergent and food industries (DasSarma and Arora, 2001). However, esterases and lipases have also been useful in laundry detergents for the removal of oil stains and are widely used as biocatalysts because of their ability to produce pure compounds. Likewise, amylases are used industrially in the first step of the production of high fructose corn syrup (hydrolysis of corn starch). They are also used in the textile industry in the de-sizing process and added to laundry detergents. Furthermore, for the environmental applications, the use of halophiles for bioremediation and biodegradation of various materials from industrial effluents to soil contaminants and accidental spills are being widely explored. In addition to enzymes, halophilic / halotolerants microorganisms living in saline environments, offer another potential applications in various fields of biotechnology like the production of biosurfactant. Biosurfactants are amphiphilic compounds synthesized from plants and microorganisms. They reduce surface tension and interfacial tension between individual molecules at the surface and interface respectively (Akbari et al., 2018). Comparing to the chemical surfactant, biosurfactant are promising alternative molecules due to their low toxicity, high biodegradability, environmental capability, mild production conditions, lower critical micelle concentration, higher selectivity, availability of resources and ability to function in wide ranges of pH, temperature and salinity (Rocha et al., 1992). They are used in various industries which include pharmaceuticals, petroleum, food, detergents, cosmetics, paints, paper products and water treatment (Akbari et al., 2018). The search for biosurfactants in extremophiles is particularly promising since these biomolecules can adapt and be stable in the harsh environments in which they are to be applied in biotechnology.OBJECTIVESEastern Algeria features numerous ecosystems including hypersaline environments, which are an important source of salt for food. The microbial diversity in Chott Tinsilt, a shallow Salt Lake with more than 200g/L salt concentration and a superficies of 2.154 Ha, has never yet been studied. The purpose of this research was to chemically analyse water samples collected from the Chott, isolate novel extremely or moderate halophilic Bacteria, and examine their phenotypic and phylogenetic characteristics with a view to screening for biosurfactants and enzymes of industrial interest.MATERIALS AND METHODSStudy area: The area is at 5 km of the Commune of Souk-Naâmane and 17 km in the South of the town of Aïn-Melila. This area skirts the trunk road 3 serving Constantine and Batna and the railway Constantine-Biskra. It is part the administrative jurisdiction of the Wilaya of Oum El Bouaghi. The Chott belongs to the wetlands of the High Plains of Constantine with a depth varying rather regularly without never exceeding 0.5 meter. Its length extends on 4 km with a width of 2.5 km (figure 1).Water samples and physico-chemical analysis: In February 2013, water samples were collected from various places at the Chott Tinsilt using Global Positioning System (GPS) coordinates of 35°53’14” N lat. and 06°28’44”E long. Samples were collected randomly in sterile polythene bags and transported immediately to the laboratory for isolation of halophilic microorganisms. All samples were treated within 24 h after collection. Temperature, pH and salinity were measured in situ using a multi-parameter probe (Hanna Instruments, Smithfield, RI, USA). The analytical methods used in this study to measure ions concentration (Ca2+, Mg2+, Fe2+, Na+, K+, Cl−, HCO3−, SO42−) were based on 4500-S-2 F standard methods described elsewhere (Association et al., 1920).Isolation of halophilic bacteria from water sample: The media (M1) used in the present study contain (g/L): 2.0 g of KCl, 100.0/200.0 g of NaCl, 1.0 g of MgSO4.7HO2, 3.0 g of Sodium Citrate, 0.36 g of MnCl2, 10.0 g of yeast extract and 15.0 g agar. The pH was adjusted to 8.0. Different dilutions of water samples were added to the above medium and incubated at 30°C during 2–7 days or more depending on growth. Appearance and growth of halophilic bacteria were monitored regularly. The growth was diluted 10 times and plated on complete medium agar (g/L): glucose 10.0; peptone 5.0; yeast extract 5.0; KH2PO4 5.0; agar 30.0; and NaCl 100.0/200.0. Resultant colonies were purified by repeated streaking on complete media agar. The pure cultures were preserved in 20% glycerol vials and stored at −80°C for long-term preservation.Biochemical characterisation of halophilic bacterial isolates: Bacterial isolates were studied for Gram’s reaction, cell morphology and pigmentation. Enzymatic assays (catalase, oxidase, nitrate reductase and urease), and assays for fermentation of lactose and mannitol were done as described by Smibert (1994).Optimization of growth conditions: Temperature, pH, and salt concentration were optimized for the growth of halophilic bacterial isolates. These growth parameters were studied quantitatively by growing the bacterial isolates in M1 medium with shaking at 200 rpm and measuring the cell density at 600 nm after 8 days of incubation. To study the effect of NaCl on the growth, bacterial isolates were inoculated on M1 medium supplemented with different concentration of NaCl: 1%-35% (w/v). The effect of pH on the growth of halophilic bacterial strains was studied by inoculating isolates on above described growth media containing NaCl and adjusted to acidic pH of 5 and 6 by using 1N HCl and alkaline pH of 8, 9, 10, 11 and 12 using 5N NaOH. The effect of temperature was studied by culturing the bacterial isolates in M1 medium at different temperatures of incubation (4°C–55°C).Screening of halophilic bacteria for hydrolytic enzymes: Hydrolase producing bacteria among the isolates were screened by plate assay on starch, tributyrin, gelatin and DNA agar plates respectively for amylase, lipase, protease and DNAse activities. Amylolytic activity of the cultures was screened on starch nutrient agar plates containing g/L: starch 10.0; peptone 5.0; yeast extract 3.0; agar 30.0; NaCl 100.0/250.0. The pH was 7.0. After incubation at 30 ºC for 7 days, the zone of clearance was determined by flooding the plates with iodine solution. The potential amylase producers were selected based on ratio of zone of clearance diameter to colony diameter. Lipase activity of the cultures was screened on tributyrin nutrient agar plates containing 1% (v/v) of tributyrin. Isolates that showed clear zones of tributyrin hydrolysis were identified as lipase producing bacteria. Proteolytic activity of the isolates was similarly screened on gelatin nutrient agar plates containing 10.0 g/L of gelatin. The isolates showing zones of gelatin clearance upon treatment with acidic mercuric chloride were selected and designated as protease producing bacteria. The presence of DNAse activity on plates was determined on DNAse test agar (BBL) containing 10%-25% (w/v) total salt. After incubation for 7days, the plates were flooded with 1N HCl solution. Clear halos around the colonies indicated DNAse activity (Jeffries et al., 1957).Milk clotting activity (coagulase activity) of the isolates was also determined following the procedure described (Berridge, 1952). Skim milk powder was reconstituted in 10 mM aqueous CaCl2 (pH 6.5) to a final concentration of 0.12 kg/L. Enzyme extracts were added at a rate of 0.1 mL per mL of milk. The coagulation point was determined by manual rotating of the test tube periodically, at short time intervals, and checking for visible clot formation.Screening of halophilic bacteria for biosurfactant production. Oil spread Assay: The Petridis base was filled with 50 mL of distilled water. On the water surface, 20μL of diesel and 10μl of culture were added respectively. The culture was introduced at different spots on the diesel, which is coated on the water surface. The occurrence of a clear zone was an indicator of positive result (Morikawa et al., 2000). The diameter of the oil expelling circles was measured by slide caliber (with a degree of accuracy of 0.02 mm).Surface tension and emulsification index (E24): Isolates were cultivated at 30 °C for 7 days on the enrichment medium containing 10-25% NaCl and diesel oil as the sole carbon source. The medium was centrifuged (7000 rpm for 20 min) and the surface tension of the cell-free culture broth was measured with a TS90000 surface tensiometer (Nima, Coventry, England) as a qualitative indicator of biosurfactant production. The culture broth was collected with a Pasteur pipette to remove the non-emulsified hydrocarbons. The emulsifying capacity was evaluated by an emulsification index (E24). The E24 of culture samples was determined by adding 2 mL of diesel oil to the same amount of culture, mixed for 2 min with a vortex, and allowed to stand for 24 h. E24 index is defined as the percentage of height of emulsified layer (mm) divided by the total height of the liquid column (mm).Biosurfactant stability studies : After growth on diesel oil as sole source of carbone, cultures supernatant obtained after centrifugation at 6,000 rpm for 15 min were considered as the source of crude biosurfactant. Its stability was determined by subjecting the culture supernatant to various temperature ranges (30, 40, 50, 60, 70, 80 and 100 °C) for 30 min then cooled to room temperature. Similarly, the effect of different pH (2–11) on the activity of the biosurfactant was tested. The activity of the biosurfactant was investigated by measuring the emulsification index (El-Sersy, 2012).Molecular identification of potential strains. DNA extraction and PCR amplification of 16S rDNA: Total cellular DNA was extracted from strains and purified as described by Sambrook et al. (1989). DNA was purified using Geneclean® Turbo (Q-BIO gene, Carlsbad, CA, USA) before use as a template in polymerase chain reaction (PCR) amplification. For the 16S rDNA gene sequence, the purified DNA was amplified using a universal primer set, forward primer (27f; 5′-AGA GTT TGA TCM TGG CTC AG) and a reverse primer (1492r; 5′-TAC GGY TAC CTT GTT ACG ACT T) (Lane, 1991). Agarose gel electrophoresis confirmed the amplification product as a 1400-bp DNA fragment.16S rDNA sequencing and Phylogenic analysis: Amplicons generated using primer pair 27f-1492r was sequenced using an automatic sequencer system at Macrogene Company (Seoul, Korea). The sequences were compared with those of the NCBI BLAST GenBank nucleotide sequence databases. Phylogenetic trees were constructed by the neighbor-joining method using MEGA version 5.05 software (Tamura et al., 2011). Bootstrap resembling analysis for 1,000 replicates was performed to estimate the confidence of tree topologies.Nucleotide sequence accession numbers: The nucleotide sequences reported in this work have been deposited in the EMBL Nucleotide Sequence Database. The accession numbers are represented in table 5.Statistics: All experiments were conducted in triplicates. Results were evaluated for statistical significance using ANOVA.RESULTSPhysico-chemical parameters of the collected water samples: The physicochemical properties of the collected water samples are reported in table 1. At the time of sampling, the temperature was 10.6°C and pH 7.89. The salinity of the sample, as determined in situ, was 224.70 g/L (22,47% (w/v)). Chemical analysis of water sample indicated that Na +and Cl- were the most abundant ions (table 1). SO4-2 and Mg+2 was present in much smaller amounts compared to Na +and Cl- concentration. Low levels of calcium, potassium and bicarbonate were also detected, often at less than 1 g/L.Characterization of isolates. Morphological and biochemical characteristic feature of halophilic bacterial isolates: Among 52 strains isolated from water of Chott Tinsilt, seven distinct bacteria (A1, A2, A3, A4, B1, B4 and B5) were chosen for further characterization (table 2). The colour of the isolates varied from beige, pale yellow, yellowish and orange. The bacterial isolates A1, A2, A4, B1 and B5 were rod shaped and gram negative (except B5), whereas A3 and B4 were cocci and gram positive. All strains were oxidase and catalase positive except for B1. Nitrate reductase and urease activities were observed in all the bacterial isolates, except B4. All the bacterial isolates were negative for H2S formation. B5 was the only strain positive for mannitol fermentation (table 2).We isolated halophilic bacteria on growth medium with NaCl supplementation at pH 7 and temperature of 30°C. We studied the effect of NaCl, temperature and pH on the growth of bacterial isolates. All the isolates exhibited growth only in the presence of NaCl indicating that these strains are halophilic. The optimum growth of isolates A3 and B1 was observed in the presence of 10% NaCl, whereas it was 15% NaCl for A1, A2 and B5. A4 and B4 showed optimum growth in the presence of 20% and 25% NaCl respectively. A4, B4 and B5 strains can tolerate up to 35% NaCl.The isolate B1 showed growth in medium supplemented with 10% NaCl and pH range of 7–10. The optimum pH for the growth B1 was 9 and they did not show any detectable growth at or below pH 6 (table 2), which indicates the alkaliphilic nature of B1 isolate. The bacterial isolates A1, A2 and A4 exhibited growth in the range of pH 6–10, while A3 and B4 did not show any growth at pH greater than 8. The optimum pH for growth of all strains (except B1) was pH 7.0 (table 2). These results indicate that A1, A2, A3, A4, B4 and B5 are neutrophilic in nature. All the bacterial isolates exhibited optimal growth at 30°C and no detectable growth at 55°C. Also, detectable growth of isolates A1, A2 and A4 was observed at 4°C. However, none of the bacterial strains could grow below 4°C and above 50°C (table 2).Screening of the halophilic enzymes: To characterize the diversity of halophiles able to produce hydrolytic enzymes among the population of microorganisms inhabiting the hypersaline habitats of East Algeria (Chott Tinsilt), a screening was performed. As described in Materials and Methods, samples were plated on solid media containing 10%-25% (w/v) of total salts and different substrates for the detection of amylase, protease, lipase and DNAse activities. However, coagulase activity was determined in liquid medium using milk as substrate (figure 3). Distributions of hydrolytic activity among the isolates are summarized in table 4.From the seven bacterial isolates, four strains A1, A2, A4 and B5 showed combined hydrolytic activities. They were positive for gelatinase, lipase and coagulase. A3 strain showed gelatinase and lipase activities. DNAse activities were detected with A1, A4, B1 and B5 isolates. B4 presented lipase and coagulase activity. Surprisingly, no amylase activity was detected among all the isolates.Screening for biosurfactant producing isolates: Oil spread assay: The results showed that all the strains could produce notable (>4 cm diameter) oil expelling circles (ranging from 4.11 cm to 4.67 cm). The average diameter for strain B5 was 4.67 cm, significantly (P < 0.05) higher than for the other strains.Surface tension and emulsification index (E24): The assimilation of hydrocarbons as the sole sources of carbon by the isolate strains led to the production of biosurfactants indicated by the emulsification index and the lowering of the surface tension of cell-free supernatant. Based on rapid growth on media containing diesel oil as sole carbon source, the seven isolates were tested for biosurfactant production and emulsification activity. The obtained values of the surface tension measurements as well as the emulsification index (E24) are shown in table 3. The highest reduction of surface tension was achieved with B5 and A3 isolates with values of 25.3 mN m−1 and 28.1 mN m−1 respectively. The emulsifying capacity evaluated by the E24 emulsification index was highest in the culture of isolate B4 (78%), B5 (77%) and A3 (76%) as shown in table 3 and figure 2. These emulsions were stable even after 4 months. The bacteria with emulsification indices higher than 50 % and/or reduction in the surface tension (under 30 mN/m) have been defined as potential biosurfactant producers. Based on surface tension and the E24 index results, isolates B5, B4, A3 and A4 are the best candidates for biosurfactant production. It is important to note that, strains B4 and A4 produce biosurfactant in medium containing respectively 25% and 20% (w/v) NaCl.Stability of biosurfactant activities: The applicability of biosurfactants in several biotechnological fields depends on their stability at different environmental conditions (temperatures, pH and NaCl). For this study, the strain B4 appear very interesting (It can produce biosurfactant at 25 % NaCl) and was choosen for futher analysis for biosurfactant stability. The effects of temperature and pH on the biosurfactant production by the strain B4 are shown in figure 4.biosurfactant in medium containing respectively 25% and 20% (w/v) NaCl.Stability of biosurfactant activities: The applicability of biosurfactants in several biotechnological fields depends on their stability at different environmental conditions (temperatures, pH and NaCl). For this study, the strain B4 appear very interesting (It can produce biosurfactant at 25 % NaCl) and was chosen for further analysis for biosurfactant stability. The effects of temperature and pH on the biosurfactant production by the strain B4 are shown in figure 4. The biosurfactant produced by this strain was shown to be thermostable giving an E-24 Index value greater than 78% (figure 4A). Heating of the biosurfactant to 100 °C caused no significant effect on the biosurfactant performance. Therefore, the surface activity of the crude biosurfactant supernatant remained relatively stable to pH changes between pH 6 and 11. At pH 11, the value of E24 showed almost 76% activity, whereas below pH 6 the activity was decreased up to 40% (figure 4A). The decreases of the emulsification activity by decreasing the pH value from basic to an acidic region; may be due to partial precipitation of the biosurfactant. This result indicated that biosurfactant produced by strain B4 show higher stability at alkaline than in acidic conditions.Molecular identification and phylogenies of potential isolates: To identify halophilic bacterial isolates, the 16S rDNA gene was amplified using gene-specific primers. A PCR product of ≈ 1.3 kb was detected in all the seven isolates. The 16S rDNA amplicons of each bacterial isolate was sequenced on both strands using 27F and 1492R primers. The complete nucleotide sequence of 1336,1374, 1377,1313, 1305,1308 and 1273 bp sequences were obtained from A1, A2, A3, A4, B1, B4 and B5 isolates respectively, and subjected to BLAST analysis. The 16S rDNA sequence analysis showed that the isolated strains belong to the genera Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus as shown in table 5. The halophilic isolates A2 and A4 showed 97% similarity with the Halomonas variabilis strain GSP3 (accession no. AY505527) and the Halomonas sp. M59 (accession no. AM229319), respectively. As for A1, it showed 96% similarity with the Halomonas venusta strain GSP24 (accession no. AY553074). B1 and B4 showed for their part 96% similarity with the Salinivibrio costicola subsp. alcaliphilus strain 18AG DSM4743 (accession no. NR_042255) and the Planococcus citreus (accession no. JX122551), respectively. The bacterial isolate B5 showed 98% sequence similarity with the Halobacillus trueperi (accession no. HG931926), As for A3, it showed only 95% similarity with the Staphylococcus arlettae (accession no. KR047785). The 16S rDNA nucleotide sequences of all the seven halophilic bacterial strains have been submitted to the NCBI GenBank database under the accession number presented in table 5. The phylogenetic association of the isolates is shown in figure 5.DICUSSIONThe physicochemical properties of the collected water samples indicated that this water was relatively neutral (pH 7.89) similar to the Dead Sea and the Great Salt Lake (USA) and in contrast to the more basic lakes such as Lake Wadi Natrun (Egypt) (pH 11) and El Golea Salt Lake (Algeria) (pH 9). The salinity of the sample was 224.70 g/L (22,47% (w/v). This range of salinity (20-30%) for Chott Tinsilt is comparable to a number of well characterized hypersaline ecosystems including both natural and man-made habitats, such as the Great Salt Lake (USA) and solar salterns of Puerto Rico. Thus, Chott Tinsilt is a hypersaline environment, i.e. environments with salt concentrations well above that of seawater. Chemical analysis of water sample indicated that Na +and Cl- were the most abundant ions, as in most hypersaline ecosystems (with some exceptions such as the Dead Sea). These chemical water characteristics were consistent with the previously reported data in other hypersaline ecosystems (DasSarma and Arora, 2001; Oren, 2002; Hacěne et al., 2004). Among 52 strains isolated from this Chott, seven distinct bacteria (A1, A2, A3, A4, B1, B4 and B5) were chosen for phenotypique, genotypique and phylogenetique characterization.The 16S rDNA sequence analysis showed that the isolated strains belong to the genera Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus. Genera obtained in the present study are commonly occurring in various saline habitats across the globe. Staphylococci have the ability to grow in a wide range of salt concentrations (Graham and Wilkinson, 1992; Morikawa et al., 2009; Roohi et al., 2014). For example, in Pakistan, Staphylococcus strains were isolated from various salt samples during the study conducted by Roohi et al. (2014) and these results agreed with previous reports. Halomonas, halophilic and/or halotolerant Gram-negative bacteria are typically found in saline environments (Kim et al., 2013). The presence of Planococcus and Halobacillus has been reported in studies about hypersaline lakes; like La Sal del Rey (USA) (Phillips et al., 2012) and Great Salt Lake (Spring et al., 1996), respectively. The Salinivibrio costicola was a representative model for studies on osmoregulatory and other physiological mechanisms of moderately halophilic bacteria (Oren, 2006).However, it is interesting to note that all strains shared less than 98.7% identity (the usual species cut-off proposed by Yarza et al. (2014) with their closest phylogenetic relative, suggesting that they could be considered as new species. Phenotypic, genetic and phylogenetic analyses have been suggested for the complete identification of these strains. Theses bacterial strains were tested for the production of industrially important enzymes (Amylase, protease, lipase, DNAse and coagulase). These isolates are good candidates as sources of novel enzymes with biotechnological potential as they can be used in different industrial processes at high salt concentration (up to 25% NaCl for B4). Prominent amylase, lipase, protease and DNAase activities have been reported from different hypersaline environments across the globe; e.g., Spain (Sánchez‐Porro et al., 2003), Iran (Rohban et al., 2009), Tunisia (Baati et al., 2010) and India (Gupta et al., 2016). However, to the best of our knowledge, the coagulase activity has never been detected in extreme halophilic bacteria. Isolation and characterization of crude enzymes (especially coagulase) to investigate their properties and stability are in progress.The finding of novel enzymes with optimal activities at various ranges of salt concentrations is of great importance. Besides being intrinsically stable and active at high salt concentrations, halophilic and halotolerant enzymes offer great opportunities in biotechnological applications, such as environmental bioremediation (marine, oilfiel) and food processing. The bacterial isolates were also characterized for production of biosurfactants by oil-spread assay, measurement of surface tension and emulsification index (E24). There are few reports on biosurfactant producers in hypersaline environments and in recent years, there has been a greater increase in interest and importance in halophilic bacteria for biomolecules (Donio et al., 2013; Sarafin et al., 2014). Halophiles, which have a unique lipid composition, may have an important role to play as surface-active agents. The archae bacterial ether-linked phytanyl membrane lipid of the extremely halophilic bacteria has been shown to have surfactant properties (Post and Collins, 1982). Yakimov et al. (1995) reported the production of biosurfactant by a halotolerant Bacillus licheniformis strain BAS 50 which was able to produce a lipopeptide surfactant when cultured at salinities up to 13% NaCl. From solar salt, Halomonas sp. BS4 and Kocuria marina BS-15 were found to be able to produce biosurfactant when cultured at salinities of 8% and 10% NaCl respectively (Donio et al., 2013; Sarafin et al., 2014). In the present work, strains B4 and A4 produce biosurfactant in medium containing respectively 25% and 20% NaCl. To our knowledge, this is the first report on biosurfactant production by bacteria under such salt concentration. Biosurfactants have a wide variety of industrial and environmental applications (Akbari et al., 2018) but their applicability depends on their stability at different environmental conditions. The strain B4 which can produce biosurfactant at 25% NaCl showed good stability in alkaline pH and at a temperature range of 30°C-100°C. Due to the enormous utilization of biosurfactant in detergent manufacture the choice of alkaline biosurfactant is researched (Elazzazy et al., 2015). On the other hand, the interesting finding was the thermostability of the produced biosurfactant even after heat treatment (100°C for 30 min) which suggests the use of this biosurfactant in industries where heating is of a paramount importance (Khopade et al., 2012). To date, more attention has been focused on biosurfactant producing bacteria under extreme conditions for industrial and commercial usefulness. In fact, the biosurfactant produce by strain B4 have promising usefulness in pharmaceutical, cosmetics and food industries and for bioremediation in marine environment and Microbial enhanced oil recovery (MEOR) where the salinity, temperature and pH are high.CONCLUSIONThis is the first study on the culturable halophilic bacteria community inhabiting Chott Tinsilt in Eastern Algeria. Different genera of halotolerant bacteria with different phylogeneticaly characteristics have been isolated from this Chott. Culturing of bacteria and their molecular analysis provides an opportunity to have a wide range of cultured microorganisms from extreme habitats like hypersaline environments. Enzymes produced by halophilic bacteria show interesting properties like their ability to remain functional in extreme conditions, such as high temperatures, wide range of pH, and high salt concentrations. These enzymes have great economical potential in industrial, agricultural, chemical, pharmaceutical, and biotechnological applications. Thus, the halophiles isolated from Chott Tinsilt offer an important potential for application in microbial and enzyme biotechnology. In addition, these halo bacterial biosurfactants producers isolated from this Chott will help to develop more valuable eco-friendly products to the pharmacological and food industries and will be usefulness for bioremediation in marine environment and petroleum industry.ACKNOWLEDGMENTSOur thanks to Professor Abdelhamid Zoubir for proofreading the English composition of the present paper.CONFLICT OF INTERESTThe authors declare that they have no conflict of interest.Akbari, S., N. H. Abdurahman, R. M. Yunus, F. Fayaz and O. R. Alara, 2018. Biosurfactants—a new frontier for social and environmental safety: A mini review. Biotechnology research innovation, 2(1): 81-90.Association, A. P. H., A. W. W. Association, W. P. C. Federation and W. E. Federation, 1920. Standard methods for the examination of water and wastewater. American Public Health Association.Baati, H., R. Amdouni, N. Gharsallah, A. Sghir and E. Ammar, 2010. Isolation and characterization of moderately halophilic bacteria from tunisian solar saltern. Current microbiology, 60(3): 157-161.Berridge, N., 1952. Some observations on the determination of the activity of rennet. Analyst, 77(911): 57b-62.DasSarma, S. and P. Arora, 2001. Halophiles. Encyclopedia of life sciences. Nature publishishing group: 1-9.Donio, M. B. S., F. A. Ronica, V. T. Viji, S. Velmurugan, J. S. C. A. Jenifer, M. Michaelbabu, P. Dhar and T. Citarasu, 2013. Halomonas sp. Bs4, a biosurfactant producing halophilic bacterium isolated from solar salt works in India and their biomedical importance. SpringerPlus, 2(1): 149.El-Sersy, N. A., 2012. Plackett-burman design to optimize biosurfactant production by marine Bacillus subtilis n10. Roman biotechnol lett, 17(2): 7049-7064.Elazzazy, A. M., T. Abdelmoneim and O. Almaghrabi, 2015. Isolation and characterization of biosurfactant production under extreme environmental conditions by alkali-halo-thermophilic bacteria from Saudi Arabia. Saudi journal of biological Sciences, 22(4): 466-475.Graham, J. E. and B. Wilkinson, 1992. Staphylococcus aureus osmoregulation: Roles for choline, glycine betaine, proline, and taurine. Journal of bacteriology, 174(8): 2711-2716.Gupta, S., P. Sharma, K. Dev and A. Sourirajan, 2016. Halophilic bacteria of lunsu produce an array of industrially important enzymes with salt tolerant activity. Biochemistry research international, 1: 1-10.Gupta, S., P. Sharma, K. Dev, M. Srivastava and A. Sourirajan, 2015. A diverse group of halophilic bacteria exist in lunsu, a natural salt water body of Himachal Pradesh, India. SpringerPlus 4(1): 274.Hacěne, H., F. Rafa, N. Chebhouni, S. Boutaiba, T. Bhatnagar, J. C. Baratti and B. Ollivier, 2004. Biodiversity of prokaryotic microflora in el golea salt lake, Algerian Sahara. Journal of arid environments, 58(3): 273-284.Jeffries, C. D., D. F. Holtman and D. G. Guse, 1957. Rapid method for determining the activity of microorgan-isms on nucleic acids. Journal of bacteriology, 73(4): 590.Karan, R. and S. Khare, 2010. Purification and characterization of a solvent‐stable protease from Geomicrobium sp. Emb2. Environmental technology, 31(10): 1061-1072.Khopade, A., R. Biao, X. Liu, K. Mahadik, L. Zhang and C. Kokare, 2012. Production and stability studies of the biosurfactant isolated from marine Nocardiopsis sp. B4. Desalination, 3: 198-204.Kim, K. K., J.-S. Lee and D. A. Stevens, 2013. Microbiology and epidemiology of Halomonas species. Future microbiology, 8(12): 1559-1573.Lane, D., 1991. 16s/23s rRNA sequencing in nucleic acid techniques in bacterial systematics. Stackebrandt e., editor;, and goodfellow m., editor. Chichester, UK: John Wiley & Sons.Morikawa, K., R. L. Ohniwa, T. Ohta, Y. Tanaka, K. Takeyasu and T. Msadek, 2009. Adaptation beyond the stress response: Cell structure dynamics and population heterogeneity in Staphylococcus aureus. Microbes environments, 25: 75-82.Morikawa, M., Y. Hirata and T. J. B. e. B. A.-M. Imanaka, 2000. A study on the structure–function relationship of lipopeptide biosurfactants. Biochimica et biophysica acta, 1488(3): 211-218.Oren, A., 2002. Diversity of halophilic microorganisms: Environments, phylogeny, physiology, and applications. Journal of industrial microbiology biotechnology, 28(1): 56-63.Oren, A., 2006. Halophilic microorganisms and their environments. Springer science & business media.Oren, A., R. Vreeland and L. Hochstein, 1993. Ecology of extremely halophilic microorganisms. The biology of halophilic bacteria, 2(1): 1-8.Phillips, K., F. Zaidan, O. R. Elizondo and K. L. Lowe, 2012. Phenotypic characterization and 16s rDNA identification of culturable non-obligate halophilic bacterial communities from a hypersaline lake, la sal del rey, in extreme south texas (USA). Aquatic biosystems, 8(1): 1-5.Post, F. and N. Collins, 1982. A preliminary investigation of the membrane lipid of Halobacterium halobium as a food additive 1. Journal of food biochemistry, 6(1): 25-38.Rocha, C., F. San-Blas, G. San-Blas and L. Vierma, 1992. Biosurfactant production by two isolates of Pseudomonas aeruginosa. World Journal of microbiology biotechnology, 8(2): 125-128.Rohban, R., M. A. Amoozegar and A. Ventosa, 2009. Screening and isolation of halophilic bacteria producing extracellular hydrolyses from howz soltan lake, Iran. Journal of industrial microbiology biotechnology, 36(3): 333-340.Roohi, A., I. Ahmed, N. Khalid, M. Iqbal and M. Jamil, 2014. Isolation and phylogenetic identification of halotolerant/halophilic bacteria from the salt mines of Karak, Pakistan. International journal of agricultural and biology, 16: 564-570.Sambrook, J., E. F. Fritsch and T. Maniatis, 1989. Molecular cloning: A laboratory manual, 2nd edn. Cold spring harbor laboratory, cold spring harbor, New York.Sánchez‐Porro, C., S. Martin, E. Mellado and A. Ventosa, 2003. Diversity of moderately halophilic bacteria producing extracellular hydrolytic enzymes. Journal of applied microbiology, 94(2): 295-300.Sarafin, Y., M. B. S. Donio, S. Velmurugan, M. Michaelbabu and T. Citarasu, 2014. Kocuria marina bs-15 a biosurfactant producing halophilic bacteria isolated from solar salt works in India. Saudi journal of biological sciences, 21(6): 511-519.Smibert, R., 1994. Phenotypic characterization. In methods for general and molecular bacteriology. American society for microbiology: 611-651.Solomon, E. and K. J. I. Viswalingam, 2013. Isolation, characterization of halotolerant bacteria and its biotechnological potentials. International journal scientific research paper publication sites, 4: 1-7.Spring, S., W. Ludwig, M. Marquez, A. Ventosa and K.-H. Schleifer, 1996. Halobacillus gen. Nov., with descriptions of Halobacillus litoralis sp. Nov. and Halobacillus trueperi sp. Nov., and transfer of Sporosarcina halophila to Halobacillus halophilus comb. Nov. International journal of systematic evolutionary microbiology, 46(2): 492-496.Tamura, K., D. Peterson, N. Peterson, G. Stecher, M. Nei and S. Kumar, 2011. Mega5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular biology evolution, 28(10): 2731-2739.Yakimov, M. M., K. N. Timmis, V. Wray and H. L. Fredrickson, 1995. Characterization of a new lipopeptide surfactant produced by thermotolerant and halotolerant subsurface Bacillus licheniformis bas50. Applied and environmental microbiology, 61(5): 1706-1713.Yarza, P., P. Yilmaz, E. Pruesse, F. O. Glöckner, W. Ludwig, K.-H. Schleifer, W. B. Whitman, J. Euzéby, R. Amann and R. Rosselló-Móra, 2014. Uniting the classification of cultured and uncultured bacteria and archaea using 16s rRNA gene sequences. Nature reviews microbiology, 12(9): 635-645

Abstract Objective To evaluate excess mortality in Brazil from January 2020 to April 2021, according to the primary causes of death registered in the Brazilian Mortality Information System (MIS). Methods Cross-sectional study with data extracted from the MIS. Excess deaths were examined by the primary cause of death according to 11 grouped causes. Autoregressive models used mortality data from 2015 to 2019 to predict expected deaths from January 2020 to April 2021. Excess deaths were calculated as the difference between the observed and the expected number of deaths. Results Total excess deaths of 370 055 were observed in the studied period, corresponding to a ratio of observed to expected of 1.14 in 2020 and 1.40 in 2021. Excess deaths were seen in three groups: symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified; other diseases of the respiratory system and coronavirus infection, unspecified site. Conclusions The excess mortality in Brazil in these 16 months was 1.20 times greater than the previous year. The increase in not elsewhere classified causes and causes of death associated to COVID-19 indicate caution about the negative balance for some causes. Furthermore, the inequalities of mortality reporting systems in low- and middle-income countries in relation to underestimation of mortality still need to be addressed.

The World Health Organization defines a zoonosis as any infection naturally transmissible from vertebrate animals to humans. The pandemic of Coronavirus disease (COVID-19) caused by SARS-CoV-2 has been classified as a zoonotic disease, however, no animal reservoir has yet been found, so this classification is premature. We propose that COVID-19 should instead be classified an “emerging infectious disease (EID) of probable animal origin.” To explore if COVID-19 infection fits our proposed re-categorization vs. the contemporary definitions of zoonoses, we reviewed current evidence of infection origin and transmission routes of SARS-CoV-2 virus and described this in the context of known zoonoses, EIDs and “spill-over” events. Although the initial one hundred COVID-19 patients were presumably exposed to the virus at a seafood Market in China, and despite the fact that 33 of 585 swab samples collected from surfaces and cages in the market tested positive for SARS-CoV-2, no virus was isolated directly from animals and no animal reservoir was detected. Elsewhere, SARS-CoV-2 has been detected in animals including domesticated cats, dogs, and ferrets, as well as captive-managed mink, lions, tigers, deer, and mice confirming zooanthroponosis. Other than circumstantial evidence of zoonotic cases in mink farms in the Netherlands, no cases of natural transmission from wild or domesticated animals have been confirmed. More than 40 million human COVID-19 infections reported appear to be exclusively through human-human transmission. SARS-CoV-2 virus and COVID-19 do not meet the WHO definition of zoonoses. We suggest SARS-CoV-2 should be re-classified as an EID of probable animal origin.

Abstract Background Contrasting historical views represent the asylum as a manifestation of humanitarian and therapeutic progress or as an institution of social control designed to bolster the capitalist economic order. More extreme critics suggest it was used to incarcerate people exhibiting only political or social deviance. Methods Case notes of 200 consecutive male and female admissions to the Essex County Asylum in 1904 were inspected. The nature of presentations was classified in contemporary terms into broad categories of disorder. Outcomes were identified and differences between men and women were explored. Results We found no evidence that patients were admitted without signs of significant mental and behavioural disturbance. In total, 44% of admissions had signs of an organic condition, and these were more frequent among men. Women were admitted at a faster rate and were 1.6 times more likely to have mania or a psychotic disorder. Overall, 45.5% of patients were discharged, with 62% of patients with non-organic disorders discharged recovered or improved. Conclusions Evidence partially supports both views of the asylum. In line with other studies, there is no evidence that the asylum was used to incarcerate people who did not show significant signs of disorder, but it did provide care and containment for those who could not be accommodated elsewhere, including many with organic conditions. The asylum also had a therapeutic orientation, however, and encouraged discharge where possible. In contrast to some other studies, women were more likely to be institutionalised than men, possibly reflecting their greater economic dependency.

Abstract Background and Aims Hyperkalaemia (HK) refers to increased serum potassium concentration, with possible severe effects on health outcomes and resource utilisation. HK is prevalent in patients suffering from heart failure, chronic kidney disease (CKD) and diabetes mellitus and its risk is increased by medications, e.g. inhibitors of the renin-angiotensin-aldosterone system (RAAS). The objective of this study was to examine trends in emergency department (ED) use in patients diagnosed with HK. Method The latest available 2016 Nationwide Emergency Department Sample (NEDS) data set from the Healthcare Cost and Utilization Project was analysed to estimate the burden of ED visits in patients with HK. Patients with an ICD-10 diagnosis code E87.5 (Hyperkalaemia) or E87.8 (Other disorders of electrolyte and fluid balance, not elsewhere classified; included due to the incidence of miscoding HK) were included. The rate of comorbidities (diabetes, CKD, heart failure and hypertension) were assessed using previously validated ICD-10 codes. Results In 2016, there were an estimated 1,322,071 ED visits with a diagnosis of HK, out of which 6.7% were recorded as the primary diagnosis. The vast majority of these ED visits resulted in same hospital admission (1,075,492 hospital stays). The rate of ED visits and hospital admission were 409.1 and 332.8 per 100,000 persons respectively. The mean (SE) age was 61.8 (0.21) years and 52% were male. Patients had high rate of comorbidities: diabetes 43.1%, hypertension 62.0%, CKD 44.4%, heart failure 23.1%, non-dialysis CKD 12.1% and CKD requiring dialysis 12.1%. In patients with primary diagnosis of HK, the mean (SD) hospital length of stay was 3.3 (4.2) days and total mean (SD) hospital charges were $34,923 ($100,435). Conclusion Patients with HK represent an expensive health care burden, as well as suffering with high rates of comorbidities and ED visits. There is an urgent need for new treatment options in the acute setting to improve outcomes for patients with HK.

ObjectiveThe aim of this project was to explore changing patterns in patient refusal to transport by emergency medical services for classified heroin overdoses and possible implications on heroin overdose surveillance in Kentucky.IntroductionAs a Centers for Disease Control and Prevention Enhanced State Opioid Overdose Surveillance (ESOOS) funded state, Kentucky started utilizing Emergency Medical Services (EMS) data to increase timeliness of state data on drug overdose events in late 2016. Using developed definitions of heroin overdose for EMS emergency runs, Kentucky analyzed the patterns of refused/transported EMS runs for both statewide and local jurisdictions. Changes in EMS transportation patterns of heroin overdoses can have a dramatic impact on other surveillance systems, such as emergency department (ED) claims data or syndromic surveillance (SyS) data.MethodsAs part of the ESOOS grant, Kentucky receives all emergency-only EMS runs monthly from Kentucky Board for Emergency Medical Services, Kentucky State Ambulance Reporting System data. Heroin cases were classified based on text and medications (Narcan) administered, with comparisons to historic data discussed elsewhere (Rock & Singleton, 2018). Transportation classifications are based on EMS standard elements defining treatment with transportation vs refusal to transport to hospital and canceled runs were excluded. Initial analysis included trend analysis at state and local levels, as well as demographic comparisons of refusal vs transported heroin overdose encounters.ResultsStatewide trends in EMS heroin overdoses with refusal transport significantly increased from 5% (n=42) in 2016 quarter three to 22% (n=290) in 2018 quarter two (Fig 1). Initial demographic analysis does not show any significant difference between refusals/transported for age, gender, or race. However, there are significant differences among geographic regions in Kentucky with heroin encounter refusal proportion ranging from 3%-48% in 2018 quarter two. Specifically, one urban area (Fig 2) shows the change in proportion of refusal increasing from 15% (n=23) in 2016 quarter three to 47% (n=110) in 2018 quarter two. In this geographic area, combined refused/transported EMS heroin overdoses compared to traditional ED data demonstrates opposing heroin overdose patterns for the same local with EMS showing and increasing trend overtime and ED showing a decreasing trend (Fig 3).ConclusionsTraditional public health surveillance for heroin overdose has historically relied on ED billing data, though agencies are starting to use syndromic surveillance, too (Vivolo-Kantor et al., 2016). These systems share similar underlying ED data, albeit with different components, quality, and limitations. However, in terms of the overdose epidemic, both are limited to only heroin overdoses that result in ED hospital encounters. The recent drastic increase in refused transport can have significant impacts on heroin surveillance. Jurisdictions relying on SyS or ED data for monitoring overdose patterns and/or evaluating interventions may be significantly underestimating acute overdose occurrence in the population. This analysis highlights the importance of this preclinical data source in surveillance of the heroin epidemic.ReferencesRock, P. J., & Singleton, M. D. (2018). Assessing Definitions of Heroin Overdose in ED & EMS Data Using Hospital Billing Data, 10(1), 2579.Vivolo-Kantor, A. M., Seth, P., Gladden, ; R Matthew, Mattson, C. L., Baldwin, G. T., Kite-Powell, A., & Coletta, M. A. (2016). Morbidity and Mortality Weekly Report Vital Signs: Trends in Emergency Department Visits for Suspected Opioid Overdoses — United States, 67(9), 279–285. Retrieved from https://www.cdc.gov/mmwr/volumes/67/wr/pdfs/mm6709e1-H.pdf

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.

ObjectiveWe sought to measure the burden of emergency department (ED) visits associated with injection drug use (IDU), HIV infection, and homelessness; and the intersection of homelessness with IDU and HIV infection in Massachusetts via syndromic surveillance data.IntroductionIn Massachusetts, syndromic surveillance (SyS) data have been used to monitor injection drug use and acute opioid overdoses within EDs. Currently, Massachusetts Department of Public Health (MDPH) SyS captures over 90% of ED visits statewide. These real-time data contain rich free-text and coded clinical and demographic information used to categorize visits for population level public health surveillance.Other surveillance data have shown elevated rates of opioid overdose related ED visits, Emergency Medical Service incidents, and fatalities in Massachusetts from 2014-20171,2,3. Injection of illicitly consumed opioids is associated with an increased risk of infectious diseases, including HIV infection. An investigation of an HIV outbreak among persons reporting IDU identified homelessness as a social determinant for increased risk for HIV infection.MethodsTo accomplish our objectives staff used an existing MDPH SyS IDU syndrome definition4, developed a novel syndrome definition for HIV-related visits, and adapted Maricopa County's homelessness syndrome definition. Syndromes were applied to Massachusetts ED data through the CDC’s BioSense Platform. Visits meeting the HIV and homelessness syndromes were randomly selected and reviewed to assess accuracy; inclusion and exclusion criteria were then revised to increase specificity. The final versions of all three syndrome definitions incorporate free-text elements from the chief complaint and triage notes, as well as International Statistical Classification of Diseases and Related Health Problems, 9th (ICD-9) and 10th Revision (ICD-10) diagnostic codes. Syndrome categories were not mutually exclusive, and all reported visits occurring at Massachusetts EDs were included in the analysis.Syndromes CreatedFor the HIV infection syndrome definition, we incorporated the free-text term “HIV” in both the chief complaint and triage notes. Visit level review demonstrated that the following exclusions were needed to reduce misspellings, inclusion of partial words, and documentation of HIV testing results: “negative for HIV”, “HIV neg”, “negative test for HIV”, “hive”, “hivies”, and “vehivcle”. Additionally, the following diagnostic codes were incorporated: V65.44 (Human immunodeficiency virus [HIV] counseling), V08 (asymptomatic HIV infection status), V01.79 (contact with or exposure to other viral diseases), 795.71 (nonspecific serologic evidence of HIV), V73.89 (special screening examination for other specified viral diseases), 079.53 (HIV, type 2 [HIV-2]), Z20.6 (contact with and (suspected) exposure to HIV), Z71.7 (HIV counseling), B20 (HIV disease), Z21 (asymptomatic HIV infection status), R75 (inconclusive laboratory evidence of HIV), Z11.4 (encounter for screening for HIV), and B97.35 (HIV-2 as the cause of diseases classified elsewhere).Building on the Maricopa County homeless syndrome definition, we incorporated a variety of free-text inclusion and exclusion terms. To meet this definition visits had to mention: “homeless”, or “no housing”, or, “lack of housing”, or “without housing”, or “shelter” but not animal and domestic violence shelters. We also selected the following ICD-10 codes for homelessness and inadequate housing respectively, Z59.0 and Z59.1.We analyzed MDPH SyS data for visits occurring from January 1, 2016 through June 30, 2018. Rates per 10,000 ED visits categorized as IDU, HIV, or homeless were calculated. Subsequently, visits categorized as IDU, HIV, and meeting both IDU and HIV syndrome definitions (IDU+HIV) were stratified by homelessness.ResultsSyndrome Burden on EDThe MDPH SyS dataset contains 6,767,137 ED visits occurring during the study period. Of these, 82,819 (1.2%) were IDU-related, 13,017 (0.2%) were HIV-related, 580 (<0.01%) were related to IDU + HIV, and 42,255 visits (0.6%) were associated with homelessness.The annual rate of IDU-related visits increased 15% from 2016 through June of 2018 (from 113.63 to 130.57 per 10,000 visits); while rates of HIV-related and IDU + HIV-related visits remained relatively stable. The overall rate of visits associated with homelessness increased 47% (from 49.99 to 73.26 per 10,000 visits).Rates of IDU, HIV, and IDU + HIV were significantly higher among visits associated with homelessness. Among visits that met the homeless syndrome definition compared to those that did not: the rate of IDU-related visits was 816.0 versus 118.03 per 10,000 ED visits (X2= 547.12, p<0. 0001); the rate of visits matching the HIV syndrome definition was 145.54 versus 18.44 per 10,000 ED visits (X2= 99.33, p<0.0001); and the rate of visits meeting the IDU+HIV syndrome definition was 15.86 versus 0.76 per 10,000 visits (X2= 13.72, p= 0.0002).ConclusionsMassachusetts is experiencing an increasing burden of ED visits associated with both IDU and homelessness that parallels increases in opioid overdoses. Higher rates of both IDU and HIV-related visits were associated with homelessness. An understanding of the intersection between opioid overdoses, IDU, HIV, and homelessness can inform expanded prevention efforts, introduction of alternatives to ED care, and increase consideration of housing status during ED care.Continued surveillance for these syndromes, including collection and analysis of demographic and clinical characteristics, and geographic variations, is warranted. These data can be useful to providers and public health authorities for planning healthcare services.References1. Vivolo-Kantor AM, Seth P, Gladden RM, et al. Vital Signs: Trends in Emergency Department Visits for Suspected Opioid Overdoses — United States, July 2016–September 2017. MMWR Morbidity and Mortality Weekly Report 2018; 67(9);279–285 DOI: http://dx.doi.org/10.15585/mmwr.mm6709e12. Massachusetts Department of Public Health. Chapter 55 Data Brief: An assessment of opioid-related deaths in Massachusetts, 2011-15. 2017 August. Available from: https://www.mass.gov/files/documents/2017/08/31/data-brief-chapter-55-aug-2017.pdf3. Massachusetts Department of Public Health. MA Opioid-Related EMS Incidents 2013-September 2017. 2018 Feb. Available from: https://www.mass.gov/files/documents/2018/02/14/emergency-medical-services-data-february-2018.pdf4. Bova, M. Using emergency department (ED) syndromic surveillance to measure injection-drug use as an indicator for hepatitis C risk. Powerpoint presented at: 2017 Northeast Epidemiology Conference. 2017 Oct 18 – 20; Northampton, Massachusetts, USA.

Story spreads out through time the behaviors or bodies – the shapes – a self has been or will be, each replacing the one before. Hence a story has before and after, gain and loss. It goes somewhere…Moreover, shape or body is crucial, not incidental, to story. It carries story; it makes story visible; in a sense it is story. Shape (or visible body) is in space what story is in time. (Bynum, quoted in Garland Thomson, 113-114) Drawing on Goffman’s classic work on stigma, research documenting the existence of discrimination and bias against individuals classified as obese goes back five decades. Since Cahnman published “The Stigma of Obesity” in 1968, other researchers have well documented systematic and growing discrimination against fat people (cf. Puhl and Brownell; Puhl and Heuer; Puhl and Heuer; Fikkan and Rothblum). While weight-based stereotyping has a long history (Chang and Christakis; McPhail; Schwartz), contemporary forms of anti-fat stigma and discrimination must be understood within a social and economic context of neoliberal healthism. By neoliberal healthism (see Crawford; Crawford; Metzel and Kirkland), I refer to the set of discourses that suggest that humans are rational, self-determining actors who independently make their own best choices and are thus responsible for their life chances and health outcomes. In such a context, good health becomes associated with proper selfhood, and there are material and social consequences for those who either unwell or perceived to be unwell. While the greatest impacts of size-based discrimination are structural in nature, the interpersonal impacts are also significant. Because obesity is commonly represented (at least partially) as a matter of behavioral choices in public health, medicine, and media, to “remain fat” is to invite commentary from others that one is lacking in personal responsibility. Guthman suggests that this lack of empathy “also stems from the growing perception that obesity presents a social cost, made all the more tenable when the perception of health responsibility has been reversed from a welfare model” (1126). Because weight loss is commonly held to be a reasonable and feasible goal and yet is nearly impossible to maintain in practice (Kassierer and Angell; Mann et al.; Puhl and Heuer), fat people are “in effect, asked to do the impossible and then socially punished for failing” (Greenhalgh, 474). In this article, I explore how weight-based stigma shaped the decisions of bariatric patients to undergo weight loss surgery. In doing so, I underline the work that emotion does in circulating anti-fat stigma and in creating categories of subjects along lines of health and responsibility. As well, I highlight how fat bodies are lived and negotiated in space and place. I then explore ways in which participants take up notions of time, specifically in regard to risk, in discussing what brought them to the decision to have bariatric surgery. I conclude by arguing that it is a dynamic interaction between the material, social, emotional, discursive, and the temporal that produces not only fat embodiment, but fat subjectivity “failed”, and serves as an impetus for seeking bariatric surgery. Methods This article is based on 30 semi-structured interviews with American bariatric patients. At the time of the interview, individuals were between six months and 12 years out from surgery. After obtaining Intuitional Review Board approval, recruitment occurred through a snowball sample. All interviews were audio-taped with permission and verbatim interview transcripts were analyzed by means of a thematic analysis using Dedoose (www.dedoose.com). All names given in this article are pseudonyms. This work is part of a larger project that includes two additional interviews with bariatric surgeons as well as participant-observation research. Findings Navigating Anti-Fat Stigma In discussing what it was like to be fat, all but one of the individuals I interviewed discussed experiencing substantive size-based stigma and discrimination. Whether through overt comments, indirect remarks, dirty looks, open gawking, or being ignored and unrecognized, participants felt hurt, angry, and shamed by friends, family, coworkers, medical providers, and strangers on the street because of the size of their bodies. Several recalled being bullied and even physically assaulted by peers as children. Many described the experience of being fat or very fat as one of simultaneous hypervisibility and invisibility. One young woman, Kaia, said: “I absolutely was not treated like a person … . I was just like this object to people. Just this big, you know, thing. That’s how people treated me.” Nearly all of my participants described being told repeatedly by others, including medical professionals, that their inability to lose weight was effectively a failure of the will. They found these comments to be particularly hurtful because, in fact, they had spent years, even decades, trying to lose weight only to gain the weight back plus more. Some providers and family members seemed to take up the idea that shame could be a motivating force in weight loss. However, as research by Lewis et al.; Puhl and Huerer; and Schafer and Ferraro has demonstrated, the effect this had was the opposite of what was intended. Specifically, a number of the individuals I spoke with delayed care and avoided health-facilitating behaviors, like exercising, because of the discrimination they had experienced. Instead, they turned to health-harming practices, like crash dieting. Moreover, the internalization of shame and blame served to lower a sense of self-worth for many participants. And despite having a strong sense that something outside of personal behavior explained their escalating body weights, they deeply internalized messages about responsibility and self-control. Danielle, for instance, remarked: “Why could the one thing I want the most be so impossible for me to maintain?” It is important to highlight the work that emotion does in circulating such experiences of anti-fat stigma and discrimination. As Fraser et al have argued in their discussion on fat and emotion, the social, the emotional, and the corporeal cannot be separated. Drawing on Ahmed, they argue that strong emotions are neither interior psychological states that work between individuals nor societal states that impact individuals. Rather, emotions are constitutive of subjects and collectivities, (Ahmed; Fraser et al.). Negative emotions in particular, such as hate and fear, produce categories of people, by defining them as a common threat and, in the process, they also create categories of people who are deemed legitimate and those who are not. Thus following Fraser et al, it is possible to see that anti-fat hatred did more than just negatively impact the individuals I spoke with. Rather, it worked to produce, differentiate, and drive home categories of people along lines of health, weight, risk, responsibility, and worth. In this next section, I examine the ways in which anti-fat discrimination works at the interface of not only the discursive and the emotive, but the material as well. Big Bodies, Small Spaces When they discussed their previous lives as very fat people, all of the participants made reference to a social and built environment mismatch, or in Garland Thomson’s terms, a “misfit”. A misfit occurs “when the environment does not sustain the shape and function of the body that enters it” (594). Whereas the built environment offers a fit for the majority of bodies, Garland Thomson continues, it also creates misfits for minority forms of embodiment. While Garland Thomson’s analysis is particular to disability, I argue that it extends to fat embodiment as well. In discussing what it was like to navigate the world as fat, participants described both the physical and emotional pain entailed in living in bodies that did not fit and frequently discussed the ways in which leaving the house was always a potential, anxiety-filled problem. Whereas all of the participants I interviewed discussed such misfitting, it was notable that participants in the Greater New York City area (70% of the sample) spoke about this topic at length. Specifically, they made frequent and explicit mentions of the particular interface between their fat bodies and the Metropolitan Transit Authority (MTA), and the tightly packed spaces of the city itself. Greater New York City area participants frequently spoke of the shame and physical discomfort in having to stand on public transportation for fear that they would be openly disparaged for “taking up too much room.” Some mentioned that transit seats were made of molded plastic, indicating by design the amount of space a body should occupy. Because they knew they would require more space than what was allotted, these participants only took seats after calculating how crowded the subway or train car was and how crowded it would likely become. Notably, the decision to not take a seat was one that was made at a cost for some of the larger individuals who experienced joint pain. Many participants stated that the densely populated nature of New York City made navigating daily life very challenging. In Talia’s words, “More people, more obstacles, less space.” Participants described always having to be on guard, looking for the next obstacle. As Candice put it: “I would walk in some place and say, ‘Will I be able to fit? Will I be able to manoeuvre around these people and not bump into them?’ I was always self-conscious.” Although participants often found creative solutions to navigating the hostile environment of both the MTA and the city at large, they also identified an increasing sense of isolation that resulted from the physical discomfort and embarrassment of not fitting in. For instance, Talia rarely joined her partner and their friends on outings to movies or the theater because the seats were too tight. Similarly, Decenia would make excuses to her husband in order to avoid social situations outside of the home: “I’d say to my husband, ‘I don’t feel well, you go.’ But you know what? It was because I was afraid not to fit, you know?” The anticipatory scrutinizing described by these participants, and the anxieties it produced, echoes Kirkland’s contention that fat individuals use the technique of ‘scanning’ in order to navigate and manage hostile social and built environments. Scanning, she states, involves both literally rapidly looking over situations and places to determine accessibility, as well as a learned assessment and observation technique that allows fat people to anticipate how they will be received in new situations and new places. For my participants, worries about not fitting were more than just internal calculation. Rather, others made all too clear that fat bodies are not welcome. Nina recalled nasty looks she received from other subway riders when she attempted to sit down. Decenia described an experience on a crowded commuter train in which the woman next to her openly expressed annoyance and disgust that their thighs were touching. Talia recalled being aggressively handed a weight loss brochure by a fellow passenger. When asked to contrast their experiences living in New York City with having travelled or lived elsewhere, participants almost universally described the New York as a more difficult place to live for fat people. However, the experiences of three of the Latinas that I interviewed troubled this narrative. Katrina felt that the harassment she received in her country of origin, the Dominican Republic, was far worse than what she now experienced in the New York Metropolitan Area. Although Decenia detailed painful experiences of anti-fat stigma in New York City, she nevertheless described her life as relatively “easy” compared to what it was like in her home country of Brazil. And Denisa contrasted her neighbourhood of East Harlem with other parts of Manhattan: “In Harlem it's different. Everybody is really fat or plump – so you feel a bit more comfortable. Not everybody, but there's a mix. Downtown – there's no mix.” Collectively, their stories serve as a reminder (see Franko et al.; Grabe and Hyde) to be suspicious of over determined accounts that “Latino culture” is (or people of colour communities in general are), more accepting of larger bodies and more resistant to weight-based stigma and discrimination. Their comments also reflect arguments made by Colls, Grosz, and Garland Thomson, who have all pointed to the contingent nature between space and bodies. Colls argue that sizing is both a material and an emotional process – what size we take ourselves to be shifts in different physical and emotional contexts. Grosz suggests that there is a “mutually constitutive relationship between bodies and cities” – one that, I would add, is raced, classed, and gendered. Garland Thomson has described the relationship between bodies and space/place as “a dynamic encounter between world and flesh.” These encounters, she states, are always contingent and situated: “When the spatial and temporal context shifts, so does the fit, and with it meanings and consequences” (592). In this sense, fat is materialized differently in different contexts and in different scales – nation, state, city, neighbourhood – and the materialization of fatness is always entangled with raced, classed, and gendered social and political-economic relations. Nevertheless, it is possible to draw some structural commonalities between divergent parts of the Greater New York City Metropolitan Area. Specifically, a dense population, cramped physical spaces, inaccessible transportation and transportation funding cuts, social norms of fast paced life, and elite, raced, classed, and gendered norms of status and beauty work to materialize fatness in such a way that a ‘misfit’ is often the result for fat people who live and/or work in this area. And importantly, misfitting, as Garland Thomson argues, has consequences: it literally “casts out” when the “shape and function of … bodies comes into conflict with the shape and stuff of the built world” (594). This casting out produces some bodies as irrelevant to social and economic life, resulting in segregation and isolation. To misfit, she argues, is to be denied full citizenship. Responsibilising the Present Garland Thomson, discussing Bynum’s statement that “shape carries story”, argues the following: “the idea that shape carries story suggests … that material bodies are not only in the spaces of the world but that they are entwined with temporality as well” (596). In this section, I discuss how participants described their decisions to get weight loss surgery by making references to the need take responsibility for health now, in the present, in order to avoid further and future morbidity and mortality. Following Adams et al., I look at how the fat body is lived in a state of constant anticipation – “thinking and living toward the future” (246). All of the participants I spoke with described long histories of weight cycling. While many managed to lose weight, none were able to maintain this weight loss in the long term – a reality consistent with the medical fact that dieting does not produce durable results (Kassirer and Angell; Mann et al.; Puhl and Heuer). They experienced this inability as not only distressing, but terrifying, as they repeatedly regained the lost weight plus more. When participants discussed their decisions to have surgery, they highlighted concerns about weight related comorbidities and mobility limitations in their explanations. Consistent then with Boero, Lopez, and Wadden et al., the participants I spoke with did not seek out surgery in hopes of finding a permanent way to become thin, but rather a permanent way to become healthy and normal. Concerns about what is considered to be normative health, more than simply concerns about what is held to be an appropriate appearance, motivated their decisions. Significantly, for these participants the decision to have bariatric surgery was based on concerns about future morbidity (and mortality) at least as much, if not more so, than on concerns about a current state of ill health and impairment. Some individuals I spoke with were unquestionably suffering from multiple chronic and even life threatening illnesses and feared they would prematurely die from these conditions. Other participants, however, made the decision to have bariatric surgery despite the fact that they had no comorbidities whatsoever. Motivating their decisions was the fear that they would eventually develop them. Importantly, medial providers explicitly and repeatedly told all of these participants that lest they take drastic and immediate action, they would die. For example: Faith’s reproductive endocrinologist said: “you’re going to have diabetes by the time you’re 30; you’re going to have a stroke by the time you’re 40. And I can only hope that you can recover enough from your stroke that you’ll be able to take care of your family.” Several female participants were warned that without losing weight, they would either never become pregnant or they would die in childbirth. By contrast, participants stated that their bariatric surgeons were the first providers they had encountered to both assert that obesity was a medical condition outside of their control and to offer them a solution. Within an atmosphere in which obesity is held to be largely or entirely the result of behavioural choices, the bariatric profession thus positions itself as unique by offering both understanding and what it claims to be a durable treatment. Importantly, it would be a mistake to conclude that some bariatric patients needed surgery while others choose it for the wrong reasons. Regardless of their states of health at the time they made the decision to have surgery, the concerns that drove these patients to seek out these procedures were experienced as very real. Whether or not these concerns would have materialized as actual health conditions is unknown. Furthermore, bariatric patients should not be seen as having been duped or suffering from ‘false consciousness.’ Rather, they operate within a particular set of social, cultural, and political-economic conditions that suggest that good citizenship requires risk avoidance and personal health management. As these individuals experienced, there are material and social consequences for ‘failing’ to obtain normative conceptualizations of health. This set of conditions helps to produce a bariatric patient population that includes both those who were contending with serious health concerns and those who feared they would develop them. All bariatric patients operate within this set of conditions (as do medical providers) and make decisions regarding health (current, future, or both) by using the resources available to them. In her work on the temporalities of dieting, Coleman argues that rather than seeing dieting as a linear and progressive event, we might think of it instead a process that brings the future into the present as potential. Adams et al suggest concerns about potential futures, particularly in regard to health, are a defining characteristic of our time. They state: “The present is governed, at almost every scale, as if the future is what matters most. Anticipatory modes enable the production of possible futures that are lived and felt as inevitable in the present, rendering hope and fear as important political vectors” (249). The ability to act in the present based on potential future risks, they argue, has become a moral imperative and a marker of proper of citizenship. Importantly, however, our work to secure the ‘best possible future’ is never fully assured, as risks are constantly changing. The future is thus always uncertain. Acting responsibly in the present therefore requires “alertness and vigilance as normative affective states” (254). Importantly, these anticipations are not diagnostic, but productive. As Adams et al state, “the future arrives already formed in the present, as if the emergency has already happened…a ‘sense’ of the simultaneous uncertainty and inevitability of the future, usually manifest in entanglements of fear and hope” (250). It is in this light, then, that we might see the decision to have bariatric surgery. For these participants, their future weight-related morbidity and mortality had already arrived in the present and thus they felt they needed to act responsibly now, by undergoing what they had been told was the only durable medical intervention for obesity. The emotions of hope, fear, anxiety and I would suggest, hatred, were key in making these decisions. Conclusion Medical, public health, and media discourses frame obesity as an epidemic that threatens to bring untold financial disaster and escalating rates of morbidity and mortality upon the nation state and the world at large. As Fraser et al argue, strong emotions (such hatred, fear, anxiety, and hope), are at the centre of these discourses; they construct, circulate, and proliferate them. Moreover, they create categories of people who are deemed legitimate and categories of others who are not. In this context, the participants I spoke with were caught between a desire to have fatness understood as a medical condition needing intervention; the anti-fat attitudes of others, including providers, which held that obesity was a failure of the will and nothing more; their own internalization of these messages of personal responsibility for proper behavioural choices, and, the biologically intractable nature of fatness wherein dieting not only fails to reduce weight in the vast majority of cases but results, in the long term, in increased weight gain (Kassirer and Angell; Mann et al.; Puhl and Heuer). Widespread anxiety and embarrassment over and fear and hatred of fatness was something that the individuals I interviewed experienced directly and which signalled to them that they were less than human. Their desire for weight loss, therefore was partially a desire to become ‘normal.’ In Butler’s term, it was the desire for a ‘liveable life. ’A liveable life, for these participants, included a desire for a seamless fit with the built environment. The individuals I spoke with were never more ashamed of their fatness than when they experienced a ‘misfit’, in Garland Thomson’s terms, between their bodies and the material world. Moreover, feelings of shame over this disjuncture worked in tandem with a deeply felt, pressing sense that something must be done in the present to secure a better health future. The belief that bariatric surgery might finally provide a durable answer to obesity served as a strong motivating factor in their decisions to undergo bariatric surgery. By taking drastic action to lose weight, participants hoped to contest stigmatizing beliefs that their fat bodies reflected pathological interiors. Moreover, they sought to demonstrate responsibility and thus secure proper subjectivities and citizenship. In this sense, concerns, anxieties, and fears about health cannot be disentangled from the experience of anti-fat stigma and discrimination. Again, anti-fat bias, for these participants, was more than discursive: it operated through the circulation of emotion and was experienced in a very material sense. The decision to have weight loss surgery can thus be seen as occurring at the interface of emotion, flesh, space, place, and time, and in ways that are fundamentally shaped by the broader social context of neoliberal healthism. AcknowledgmentI am grateful to the anonymous reviewers of this article for their helpful feedback on earlier version. References Adams, Vincanne, Michelle Murphy, and Adele E. Clarke. “Anticipation: Technoscience, Life, Affect, Temporality.” Subjectivity 28.1 (2009): 246-265. Ahmed, Sara. “Affective Economies.” Social Text 22.2 (2004): 117-139 Boero, Natalie. Killer Fat: Media, Medicine, and Morals in the American "Obesity Epidemic". New Brunswick: Rutgers University Press, 2012. Butler, Judith. Undoing Gender. New York: Routledge, 2004. Bynum, Caroline Walker. 1999. Jefferson Lecture in the Humanities. National Endowment for the Humanities. Washington, DC, 1999. Cahnman, Werner J. “The Stigma of Obesity.” The Sociological Quarterly 9.3 (1968): 283-299. Chang, Virginia W., and Nicholas A. Christakis. “Medical Modeling of Obesity: A Transition from Action to Experience in a 20th Century American Medical Textbook.” Sociology of Health & Illness 24.2 (2002): 151-177. Coleman, Rebecca. “Dieting Temporalities: Interaction, Agency and the Measure of Online Weight Watching.” Time & Society 19.2 (2010): 265-285. Colls, Rachel. “‘Looking Alright, Feeling Alright:’ Emotions, Sizing, and the Geographies of Women’s Experience of Clothing Consumption.” Social & Cultural Geography 5.4 (2004): 583-596. Crawford, Robert. “You Are Dangerous to Your Health: The Ideology and Politics of Victim Blaming.” International Journal of Health Services 7.4 (1977): 663-680. ———. “Health as a Meaningful Social Practice.: Health 10.4 (2006): 401-20. Dedoose. Computer Software. n.d. Franko, Debra L., Emilie J. Coen, James P. Roehrig, Rachel Rodgers, Amy Jenkins, Meghan E. Lovering, Stephanie Dela Cruz. “Considering J. Lo and Ugly Betty: A Qualitative Examination of Risk Factors and Prevention Targets for Body Dissatisfaction, Eating Disorders, and Obesity in Young Latina Women.” Body Image 9.3 (2012), 381-387. Fikken, Janna J., and Esther D. Rothblum. “Is Fat a Feminist Issue? Exploring the Gendered Nature of Weight Bias.” Sex Roles 66.9-10 (2012): 575-592. Fraser, Suzanne, JaneMaree Maher, and Jan Wright. “Between Bodies and Collectivities: Articulating the Action of Emotion in Obesity Epidemic Discourse.” Social Theory & Health 8.2 (2010): 192-209. Garland Thomson, Rosemarie. “Misfits: A Feminist Materialist Disability Concept.” Hypatia 26.3 (2011): 591-609. Goffman, Erving. Stigma: Notes on the Management of Spoiled Identity. New York: Simon & Schuster, 1963. Grabe, Shelly, and Janet S. Hyde. “Ethnicity and Body Dissatisfaction among Women in the United States: A Meta-Analysis.” Psychological Bulletin 132.2 (2006): 622. Greenhalgh, Susan. “Weighty Subjects: The Biopolitics of the U.S. War on Fat.” American Ethnologist 39.3 (2012): 471-487. Grosz, Elizabeth A. “Bodies-Cities.” Feminist Theory and the Body: A Reader, eds. Janet Price and Margrit Shildrick. New York: Routledge, 1999. 381-387. Guthman, Julie. “Teaching the Politics of Obesity: Insights into Neoliberal Embodiment and Contemporary Biopolitics.” Antipode 41.5 (2009): 1110-1133. Kassirer, Jerome P., and M. Marcia Angell. “Losing Weight: An Ill-Fated New Year's Resolution.” The New England Journal of Medicine 338.1 (1998): 52. Kirkland, Anna. “Think of the Hippopotamus: Rights Consciousness in the Fat Acceptance Movement.” Law & Society Review 42.2 (2008): 397-432. Lewis, Sophie, Samantha L. Thomas, R. Warwick Blood, David Castle, Jim Hyde, and Paul A. Komesaroff. “How Do Obese Individuals Perceive and Respond to the Different Types of Obesity Stigma That They Encounter in Their Daily Lives? A Qualitative Study.” Social Science & Medicine 73.9 (2011): 1349-56. López, Julia Navas. “Socio-Anthropological Analysis of Bariatric Surgery Patients: A Preliminary Study.” Social Medicine 4.4 (2009): 209-217. McPhail, Deborah. “What to Do with the ‘Tubby Hubby?: ‘Obesity,’ the Crisis of Masculinity, and the Nuclear Family in Early Cold War Canada. Antipode 41.5 (2009): 1021-1050. Mann, Traci, A. Janet Tomiyama, Erika Westling, Ann-Marie Lew, Barbara Samuels, and Jason Chatman. “Medicare’s Search for Effective Obesity Treatments.” American Psychologist 62.3 (2007): 220-233. Metzl, Jonathan. “Introduction: Why ‘Against Health?’” Against Health: How Health Became the New Morality, eds. Jonathan Metzl and Anna Kirkland. New York: NYU Press, 2010. 1-14. Puhl, Rebecca M. “Obesity Stigma: Important Considerations for Public Health.” American Journal of Public Health 100.6 (2010): 1019-1028.———, and Kelly D. Brownell. “Psychosocial Origins of Obesity Stigma: Toward Changing a Powerful and Pervasive Bias.” Obesity Reviews 4.4 (2003): 213-227. ——— and Chelsea A. Heuer. “The Stigma of Obesity: A Review and Update.” Obesity 17.5 (2009): 941-964. Schafer, Markus H., and Kenneth F. Ferraro. “The Stigma of Obesity: Does Perceived Weight Discrimination Affect Identity and Physical Health?” Social Psychology Quarterly 74.1 (2011): 76-97. Schwartz, H. Never Satisfied: A Cultural History of Diets, Fantasies, and Fat. New York: Anchor Books, 1986. Wadden, Thomas A., David B. Sarwer, Anthony N. Fabricatore, LaShanda R. Jones, Rebecca Stack, and Noel Williams. “Psychosocial and Behavioral Status of Patients Undergoing Bariatric Surgery: What to Expect before and after Surgery.” The Medical Clinics of North America 91.3 (2007): 451-69. Wilson, Bianca. “Fat, the First Lady, and Fighting the Politics of Health Science.” Lecture. The Graduate Center of the City University of New York. 14 Feb. 2011.

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. Australian Antarctic Strategy and 20 Year Action Plan. Canberra: Commonwealth of Australia, 2016. 15 Apr. 2019. <http://www.antarctica.gov.au/__data/assets/pdf_file/0008/180827/20YearStrategy_final.pdf>.Australian Antarctic Division. “Australia-China Collaboration Strengthens.” Australian Antarctic Magazine 27 Dec. 2014. 15 Apr. 2019. <http://www.antarctica.gov.au/magazine/2011-2015/issue-27-december-2014/in-brief/australia-china-collaboration-strengthens>.Baker, Emily. “Worry at Premier’s Defence of China.” The Mercury 15 Sep. 2018: 9.Baldacchino, G. “Studying Islands: On Whose Terms?” Island Studies Journal 3.1 (2008): 37–56.Barker, Peter F., Gabriel M. Filippelli, Fabio Florindo, Ellen E. Martin, and Howard D. Schere. “Onset and Role of the Antarctic Circumpolar Current.” Deep Sea Research Part II: Topical Studies in Oceanography. 54.21–22 (2007): 2388–98.Bergin, Anthony. “Australia Needs to Strengthen Its Strategic Interests in Antarctica.” Australian Strategic Policy Institute. 29 Apr. 2016. 21 Feb. 2019 <https://www.aspi.org.au/index.php/opinion/australia-needs-strengthen-its-strategic-interests-antarctica>.Boyce, James. 1835: The Founding of Melbourne and the Conquest of Australia. Melbourne: Black Inc., 2011.Burden, Hilary. “Xi Jinping's Tasmania Visit May Seem Trivial, But Is Full of Strategy.” The Guardian 18 Nov. 2014. 19 May 2019 <https://www.theguardian.com/world/2014/nov/18/xi-jinpings-tasmania-visit-lacking-congruity-full-of-strategy>.Bureau of Infrastructure Transport and Regional Economics (BITRE). A Regional Economy: A Case Study of Tasmania. Canberra: Commonwealth of Australia, 2008. 14 May 2019 <http://www.bitre.gov.au/publications/86/Files/report116.pdf>.Chandler, Jo. “The Science Laboratory: From Little Things, Big Things Grow.” Griffith Review: Tasmania: The Tipping Point? 29 (2013) 83–101.Christchurch City Council. Statement of Intent between the Southern Rim Gateway Cities to the Antarctic: Ushuaia, Punta Arenas, Christchurch, Hobart and Cape Town. 25 Sep. 2009. 11 Apr. 2019 <http://archived.ccc.govt.nz/Council/proceedings/2009/September/CnclCover24th/Clause8Attachment.pdf>.Convey, P., R. Bindschadler, G. di Prisco, E. Fahrbach, J. Gutt, D.A. Hodgson, P.A. Mayewski, C.P. Summerhayes, J. Turner, and ACCE Consortium. “Antarctic Climate Change and the Environment.” Antarctic Science 21.6 (2009): 541–63.Cranston, C. “Rambling in Overdrive: Travelling through Tasmanian Literature.” Tasmanian Historical Studies 8.2 (2003): 28–39.Davies, Lynn, Margaret Davies, and Warren Boyles. Mapping Van Diemen’s Land and the Great Beyond: Rare and Beautiful Maps from the Royal Society of Tasmania. Hobart: The Royal Society of Tasmania, 2018.Department of Infrastructure and Regional Development. Guidelines for Analysing Regional Australia Impacts and Developing a Regional Australia Impact Statement. Canberra: Commonwealth of Australia, 2017. 11 Apr. 2019 <https://regional.gov.au/regional/information/rais/>.Dodds, Klaus. “Awkward Antarctic Nationalism: Bodies, Ice Cores and Gateways in and beyond Australian Antarctic Territory/East Antarctica.” Polar Record 53.1 (2016): 16–30.———. Geopolitics in Antarctica: Views from the Southern Oceanic Rim. Chichester: John Wiley, 1997.Griffiths, Tom. “The Breath of Antarctica.” Tasmanian Historical Studies 11 (2006): 4–14.Gutwein, Peter. “Antarctic Gateway Worth $186 Million to Tasmanian Economy.” Hobart: Tasmanian Government, 20 Feb. 2019. 21 Feb. 2019 <http://www.premier.tas.gov.au/releases/antarctic_gateway_worth_$186_million_to_tasmanian_economy>.Hall, C. Michael. “Polar Gateways: Approaches, Issues and Review.” The Polar Journal 5.2 (2015): 257–77. Harwood Andrew. “The Political Constitution of Islandness: The ‘Tasmanian Problem’ and Ten Days on the Island.” PhD Thesis. U of Tasmania, 2011. <http://eprints.utas.edu.au/11855/%5Cninternal-pdf://5288/11855.html>.Hay, Peter. “Destabilising Tasmanian Politics: The Key Role of the Greens.” Bulletin of the Centre for Tasmanian Historical Studies 3.2 (1991): 60–70.Hingley, Rebecca. Personal Communication, 28 Nov. 2018.Johnston, P. “Is the First Wave of Climate Migrants Landing in Hobart?” The Fifth Estate 11 Sep. 2018. 15 Mar. 2019 <https://www.thefifthestate.com.au/urbanism/climate-change-news/climate-migrants-landing-hobart>.Kriwoken, L., and J. Williamson. “Hobart, Tasmania: Antarctic and Southern Ocean Connections.” Polar Record 29.169 (1993): 93–102.Kudelka, John. “The Southerly.” Kudelka Cartoons. 27 Jun. 2014. 21 Feb. 2019 <https://www.kudelka.com.au/2014/06/the-southerly/>.Leane, E., T. Winter, and J.F. Salazar. “Caught between Nationalism and Internationalism: Replicating Histories of Antarctica in Hobart.” International Journal of Heritage Studies 22.3 (2016): 214–27. Leane, Elizabeth. “Tasmania from Below: Antarctic Travellers’ Accounts of a Southern ‘Gateway’.” Studies in Travel Writing 20.1 (2016): 34-48.Mawson’s Huts Replica Museum. “Mission Statement.” 15 Apr. 2019 <http://www.mawsons-huts-replica.org.au/>.Mercer, David. "Australia's Constitution, Federalism and the ‘Tasmanian Dam Case’." Political Geography Quarterly 4.2 (1985): 91–110.Paasi, A. “Deconstructing Regions: Notes on the Scales of Spatial Life.” Environment and Planning A: Economy and Space 23.2 (1991) 239–56.Reddit. “Maps without Tasmania.” 15 Apr. 2019 <https://www.reddit.com/r/MapsWithoutTasmania/>.Roldan, Gabriela. “'A Door to the Ice?: The Significance of the Antarctic Gateway Cities Today.” Journal of Antarctic Affairs 2 (2015): 57–70.Salazar, Juan Francisco. “Geographies of Place-Making in Antarctica: An Ethnographic Epproach.” The Polar Journal 3.1 (2013): 53–71.———, Elizabeth Leane, Liam Magee, and Paul James. “Five Cities That Could Change the Future of Antarctica.” The Conversation 5 Oct. 2016. 19 May 2019 <https://theconversation.com/five-cities-that-could-change-the-future-of-antarctica-66259>.Stratford, Elaine, Godfrey Baldacchino, Elizabeth McMahon, Carol Farbotko, and Andrew Harwood. “Envisioning the Archipelago.” Island Studies Journal 6.2 (2011): 113–30.Tasmanian Climate Change Office. Derivation of the Tasmanian Sea Level Rise Planning Allowances. Aug. 2012. 17 Apr. 2019 <http://www.dpac.tas.gov.au/__data/assets/pdf_file/0003/176331/Tasmanian_SeaLevelRisePlanningAllowance_TechPaper_Aug2012.pdf>.Tasmanian Government Department of State Growth. “Tasmanian Antarctic Gateway Strategy.” Hobart: Tasmanian Government, 12 Dec. 2017. 21 Feb. 2019 <https://www.antarctic.tas.gov.au/__data/assets/pdf_file/0004/164749/Tasmanian_Antarctic_Gateway_Strategy_12_Dec_2017.pdf>.———. “Tasmania Delivers…” Apr. 2016. 15 Apr. 2019 <https://www.antarctic.tas.gov.au/__data/assets/pdf_file/0005/66461/Tasmania_Delivers_Antarctic_Southern_Ocean_web.pdf>.———. “Antarctic Tasmania.” 17 Feb. 2019. 15 Apr. 2019 <https://www.antarctic.tas.gov.au/about/hobarts_antarctic_attractions>.Tasmanian Polar Network. “Welcome to the Tasmanian Polar Network.” 28 Feb. 2019 <https://www.tasmanianpolarnetwork.com.au/>.Terauds, Aleks, and Jasmine Lee. “Antarctic Biogeography Revisited: Updating the Antarctic Conservation Biogeographic Regions.” Diversity and Distributions 22 (2016): 836–40.Van Ommen, Tas, and Vin Morgan. “Snowfall Increase in Coastal East Antarctica Linked with Southwest Western Australian Drought.” Nature Geoscience 3 (2010): 267–72.Wells Economic Analysis. The Contribution of the Antarctic and Southern Ocean Sector to the Tasmanian Economy 2017. 18 Nov. 2018. 15 Apr. 2019 <https://www.stategrowth.tas.gov.au/__data/assets/pdf_file/0010/185671/Wells_Report_on_the_Value_of_the_Antarctic_Sector_2017_18.pdf>.West, J. “Obstacles to Progress: What’s Wrong with Tasmania, Really?” Griffith Review: Tasmania: The Tipping Point? 39 (2013): 31–53.