Use of accounting concepts to study research: return on investment in XSEDE, a US cyberinfrastructure service.

This paper uses accounting concepts-particularly the concept of Return on Investment (ROI)-to reveal the quantitative value of scientific research pertaining to a major US cyberinfrastructure project (XSEDE-the eXtreme Science and Engineering Discovery Environment). XSEDE provides operational and support services for advanced information technology systems, cloud systems, and supercomputers supporting non-classified US research, with an average budget for XSEDE of US$20M+ per year over the period studied (2014-2021). To assess the financial effectiveness of these services, we calculated a proxy for ROI, and converted quantitative measures of XSEDE service delivery into financial values using costs for service from the US marketplace. We calculated two estimates of ROI: a Conservative Estimate, functioning as a lower bound and using publicly available data for a lower valuation of XSEDE services; and a Best Available Estimate, functioning as a more accurate estimate, but using some unpublished valuation data. Using the largest dataset assembled for analysis of ROI for a cyberinfrastructure project, we found a Conservative Estimate of ROI of 1.87, and a Best Available Estimate of ROI of 3.24. Through accounting methods, we show that XSEDE services offer excellent value to the US government, that the services offered uniquely by XSEDE (that is, not otherwise available for purchase) were the most valuable to the facilitation of US research activities, and that accounting-based concepts hold great value for understanding the mechanisms of scientific research generally.

A survey of Australian public attitudes towards funding of high cost cancer medicines.

BACKGROUND: In the past decade many novel, and in some cases transformative, cancer medicines have entered the market. Their prices and the amount spent on them by governments have increased rapidly, bringing to the forefront trade-offs that must be made. In this paper we explore the Australian public's attitude towards the funding of high cost cancer medicines (HCCM) to inform reimbursement and health technology assessment (HTA) policy. METHODS: A survey consisting of 49 questions about the funding of HCCMs was developed by the investigators. Recruitment was conducted via Qualtrics. 1039 Australian adults completed the survey. RESULTS: The Australian public overwhelmingly supports funding of HCCMs (95.5 %) to enhance equity of access (97.8 %), and to respond to patients' needs (98 %). When respondents were challenged to balance equity versus access in different contexts inconsistencies emerged. Different demographic factors were important in predicting support for various strategies. CONCLUSION: Our results suggest that the Australian public strongly supports government funding of HCCMs and values both equity and access. Equally, however, the public is uncertain about how equity and access are to be balanced and achieved, and such ambivalence needs to be both further explored and accommodated in policy processes. Our results may be used by policymakers in Australia, and countries with similar systems and values, to further develop policies and processes for funding HCCMs.

Absolute Erythrocytosis in a Sunda Wrinkled Hornbill (Aceros corrugatus).

A captive, 22-year-old, intact male Sunda wrinkled hornbill (Aceros corrugatus) was presented for an acute onset of open-mouth breathing and bilaterally drooped wings. An external physical examination revealed a moderately thin body condition, marked respiratory effort, and a significant heart murmur. Diagnostic blood testing revealed moderate azotemia and persistent erythrocytosis, initially documented 2 years before this event. Radiographic imaging revealed a subjectively enlarged heart and a right dorsal coelomic cavity mass. Further diagnostic testing included an echocardiogram and ultrasound-guided fine-needle aspirate of the right coelomic cavity mass, with cytology consistent with a carcinoma. The bird was euthanatized because of the poor prognosis. Necropsy and histopathology identified right atrioventricular valve hypertrophy with severe hypertrophic and dilated cardiomyopathy of the right ventricular free wall, atherosclerosis of the great vessels and arteriosclerosis of myocardial vessels, severe hepatic extramedullary hematopoiesis, and pulmonary carcinoma of the right lung. In this case, erythrocytosis was considered a physiologic response to hypoxemia caused by the lung mass.

Context-dependent genetic architecture of Drosophila life span.

Understanding the genetic basis of variation in life span is a major challenge that is difficult to address in human populations. Evolutionary theory predicts that alleles affecting natural variation in life span will have properties that enable them to persist in populations at intermediate frequencies, such as late-life-specific deleterious effects, antagonistic pleiotropic effects on early and late-age fitness components, and/or sex- and environment-specific or antagonistic effects. Here, we quantified variation in life span in males and females reared in 3 thermal environments for the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and an advanced intercross outbred population derived from a subset of DGRP lines. Quantitative genetic analyses of life span and the micro-environmental variance of life span in the DGRP revealed significant genetic variance for both traits within each sex and environment, as well as significant genotype-by-sex interaction (GSI) and genotype-by-environment interaction (GEI). Genome-wide association (GWA) mapping in both populations implicates over 2,000 candidate genes with sex- and environment-specific or antagonistic pleiotropic allelic effects. Over 1,000 of these genes are associated with variation in life span in other D. melanogaster populations. We functionally assessed the effects of 15 candidate genes using RNA interference (RNAi): all affected life span and/or micro-environmental variance of life span in at least one sex and environment and exhibited sex-and environment-specific effects. Our results implicate novel candidate genes affecting life span and suggest that variation for life span may be maintained by variable allelic effects in heterogeneous environments.

Health Care Administrative Costs in the United States and Canada, 2017.

Background: Before Canada's single-payer reform, its payment system, health costs, and number of health administrative personnel per capita resembled those of the United States. By 1999, administration accounted for 31% of U.S. health expenditures versus 16.7% in Canada. No recent comprehensive analyses of those costs are available. Objective: To quantify 2017 spending for administration by insurers and providers. Design: Analyses of government reports, accounting data that providers file with regulators, surveys of physicians, and census-collected data on employment in health care. Setting: United States and Canada. Measurements: Insurance overhead; administrative expenditures of hospitals, physicians, nursing homes, home care agencies, and hospices. Results: U.S. insurers and providers spent $812 billion on administration, amounting to $2497 per capita (34.2% of national health expenditures) versus $551 per capita (17.0%) in Canada: $844 versus $146 on insurers' overhead; $933 versus $196 for hospital administration; $255 versus $123 for nursing home, home care, and hospice administration; and $465 versus $87 for physicians' insurance-related costs. Of the 3.2-percentage point increase in administration's share of U.S. health expenditures since 1999, 2.4 percentage points was due to growth in private insurers' overhead, mostly because of high overhead in their Medicare and Medicaid managed-care plans. Limitations: Estimates exclude dentists, pharmacies, and some other providers; accounting categories for the 2 countries differ somewhat; and methodological changes probably resulted in an underestimate of administrative cost growth since 1999. Conclusion: The gap in health administrative spending between the United States and Canada is large and widening, and it apparently reflects the inefficiencies of the U.S. private insurance-based, multipayer system. The prices that U.S. medical providers charge incorporate a hidden surcharge to cover their costly administrative burden. Primary Funding Source: None.

COMPARISON OF TWO IODINE QUANTIFICATION METHODS IN AN ARTIFICIAL SEAWATER SYSTEM HOUSING WHITE-SPOTTED BAMBOO SHARKS ( CHILOSCYLLIUM PLAGIOSUM).

Iodine is an essential micronutrient for elasmobranchs in order to prevent goiter. Preventing goiter requires bioavailable iodide: either oral iodide or maintaining adequate aquarium water iodide concentrations. The objective of this study was to determine how oral and water supplementation affected iodine (I2) and iodide (I-) concentrations in artificial seawater aquaria housing captive white-spotted bamboo sharks ( Chiloscyllium plagiosum). Daily water samples were collected and free iodine (I2) was determined using ultraviolet-absorbance spectrophotometry (a relatively simple in-house assay) and total iodide (I-) via liquid chromatography (a more time- and expertise-intense quantification method) to learn the effects of supplementation. One water system received iodine and iodide supplementation in the form of 5% Lugol's iodine solution added directly to the water, while a second water system received no supplementation. In addition, one tank of sharks in each water system received oral iodide supplementation. Results indicated that oral supplementation provides greater increases in water concentrations of bioavailable iodide (I-) than direct water supplementation. In addition, the chromatographic results suggested that iodide is present in higher concentrations in the systems not receiving water supplementation. Increased iodide concentrations were detected in water samples after water changes and after oral iodide supplementation was administered, but total iodine (I2) concentration changes were not detectable within the same time frame.

Variability in hematology of white-spotted bamboo sharks (Chiloscyllium plagiosum) in different living environments.

Elasmobranch hematology continues to reveal new peculiarities within this specialized field. This report compares total hematologic values from the same white-spotted bamboo sharks (Chiloscyllium plagiosum) housed in different environments. We compared the hemograms one year apart, using a standardized Natt-Herrick's technique. The total white blood cell (WBC) counts of the sharks were statistically different between the two time points (initial median total WBC count = 18,920 leukocytes/µl, SD = 8,108; 1 year later total WBC count = 1,815 leukocytes/µl, SD = 1,309). The packed cell volumes were additionally found to be statistically different (19%, SD = 2.9 vs. 22%, SD = 2.0). Analysis revealed the only differences between the time points were the temperature and stocking densities at which these sharks were housed. This report emphasizes the need for a thorough understanding of the husbandry of an elasmobranch prior to interpretation of a hemogram and suggests that reference intervals should be created for each environment.

The hemic response of white-spotted bamboo sharks (Chiloscyllium plagiosum) with inflammatory disease.

As elasmobranch medicine becomes more commonplace, there continues to be confusion with techniques and evaluation of the shark hemogram and it remains unknown if they are able to mount an inflammatory hemic response. The aims of this study were to compare two total white blood cell (WBC) count techniques, establish a reference interval for captive white-spotted bamboo sharks (Chiloscyllium plagiosum), and determine if elasmobranchs are capable of mounting an inflammatory hemic response. Correlation statistics were performed on hematologic results for healthy female bamboo sharks to assess the use of Natt-Herrick's and phloxine methods. Total WBC counts and differentials were obtained from males with severe traumatic clasper wounds and compared to the healthy females. We elected clasper amputation as the preferred treatment intervention and post-operative hematology was performed one month later. There was poor correlation of leukocyte counts between the two WBC count methods. Hematologic values were established for the females and males pre- and post-operatively. Males with wounds had a marked leukocytosis and heterophilia. Post-operative blood work showed a resolution of total WBC count and a trend toward resolution of the heterophilia. This study provides hematologic values for white-spotted bamboo sharks and confirms that the Natt-Herrick's method is preferred for lymphocytic species. Hematologic differences present in males with clasper wounds suggests that elasmobranchs do mount an inflammatory hemic response. Treatment via clasper amputation proved to be a safe and efficient means for clinical treatment that led to a trend toward resolution of the inflammatory leukogram. Zoo Biol. 35:251-259, 2016. © 2016 Wiley Periodicals, Inc.

The Genomic Basis of Postponed Senescence in Drosophila melanogaster.

Natural populations harbor considerable genetic variation for lifespan. While evolutionary theory provides general explanations for the existence of this variation, our knowledge of the genes harboring naturally occurring polymorphisms affecting lifespan is limited. Here, we assessed the genetic divergence between five Drosophila melanogaster lines selected for postponed senescence for over 170 generations (O lines) and five lines from the same base population maintained at a two week generation interval for over 850 generations (B lines). On average, O lines live 70% longer than B lines, are more productive at all ages, and have delayed senescence for other traits than reproduction. We performed population sequencing of pools of individuals from all B and O lines and identified 6,394 genetically divergent variants in or near 1,928 genes at a false discovery rate of 0.068. A 2.6 Mb region at the tip of the X chromosome contained many variants fixed for alternative alleles in the two populations, suggestive of a hard selective sweep. We also assessed genome wide gene expression of O and B lines at one and five weeks of age using RNA sequencing and identified genes with significant (false discovery rate < 0.05) effects on gene expression with age, population and the age by population interaction, separately for each sex. We identified transcripts that exhibited the transcriptional signature of postponed senescence and integrated the gene expression and genetic divergence data to identify 98 (175) top candidate genes in females (males) affecting postponed senescence and increased lifespan. While several of these genes have been previously associated with Drosophila lifespan, most are novel and constitute a rich resource for future functional validation.

Evaluation of the Blood Film.

Evaluation of hemic cell morphology in stained blood film may be the most important part of the hematologic evaluation of exotic animals. The blood film provides important information regarding red blood cell abnormalities, such as changes in cell shape and color, presence of inclusions, and, in the case of lower vertebrates, changes in the position of the cell nucleus. Stained blood film also provides information about changes in leukocyte numbers and morphology, and shows important hemic features of mammalian platelets and the thrombocytes of lower vertebrates. The blood film is needed in the detection and identification of blood parasites.

Evaluation of the blood film.

Evaluation of hemic cell morphology in stained blood film may be the most important part of the hematologic evaluation of exotic animals. The blood film provides important information regarding red blood cell abnormalities, such as changes in cell shape and color, presence of inclusions, and, in the case of lower vertebrates, changes in the position of the cell nucleus. Stained blood film also provides information about changes in leukocyte numbers and morphology, and shows important hemic features of mammalian platelets and the thrombocytes of lower vertebrates. The blood film is needed in the detection and identification of blood parasites.

Influence of cardiovascular absolute risk assessment on prescribing of antihypertensive and lipid-lowering medications: a cluster randomized controlled trial.

BACKGROUND: Guidelines for management of hypertension and lipids recommend using cardiovascular absolute risk (CVAR) to manage patients. This randomized controlled trial investigated the impact of CVAR assessment in family practice on management of cardiovascular risk, including prescription of antihypertensive and lipid-lowering medication. METHODS: A cluster randomized controlled trial was conducted from 2008 to 2010 in Sydney, Australia. Family practices were randomized, and patients aged 45 to 69 years were invited to participate. Intervention family physicians (FP) were trained in use of CVAR, provided with an electronic CVAR calculator, and assessed their patients' absolute risk in a dedicated consultation. Control practice patients received a general health check. Primary outcome analyzed was the proportion of patients in each group on antihypertensive and/or lipid-lowering medication at 12 months. Multilevel logistic regression was performed to explore variables influencing changes in pharmacologic therapy. RESULTS: The study recruited 36 FPs from 34 practices and 1,074 patients, of which 906 (84.4%) completed 12-month follow-up. At 12 months, there was no significant difference between the intervention and control groups in proportion of patients on antihypertensives (31.2% vs 34.3%, P = .31), but control group patients were more likely to be on lipid-lowering medications (30.2% vs 22.7%, P = .01). After multilevel analysis, this difference was not present. Intensification or reduction of pharmacologic therapy was associated with meeting treatment targets for blood pressure and lipids but not with the CVAR or intervention group. CONCLUSIONS: Single-risk factor management remains a strong influence on FP prescribing practices. Shifting to an approach based on CVAR will require more intensive intervention.

Validation of an ultrasound-guided technique to establish a liver-to-coelom ratio and a comparative analysis of the ratios among acclimated and recently wild-caught southern stingrays, Dasyatis americana.

Southern stingrays, Dasyatis americana, are a well-represented elasmobranch species in public aquaria and other facilities throughout the world. This study was conducted at a facility that experienced some mortality and replenished the collection with wild-caught stingrays. A common necropsy finding among the stingrays was a small, dark liver. The objectives of this study were to assess the reliability of an ultrasound-guided technique for establishing a liver-to-coelom ratio by calculating the approximate length of the liver with respect to the coelomic cavity length and then to compare ratios between acclimated captive and wild-caught stingrays. The ultrasound validation phase of the study measured the distance from the caudal margin of the liver to the pelvic cartilaginous girdle and compared it to the actual distance measured during the necropsy or surgery. There was no significant difference found between the ultrasound and actual distance measurements (P = 0.945). This technique was then used to establish liver-to-coelom ratios and compare two groups of stingrays, presumably under different metabolic states at different periods. Liver-to-coelom ratios were established during initial examinations as well as 8 months after cohabitation in a touch pool exhibit. There were significant differences in liver-to-coelom ratios between the two stingray groups at introduction (median difference = 30.9%, P = 0.007) and after 8 months (median difference = 20.5%, P = 0.008). There were also significant differences in the liver-to-coelom ratios within each group at introduction and at 8 months (acclimated group median difference = 20.4%, P = 0.018; wild-caught group median difference 31%, P = 0.008).

Phenotypic plasticity of the Drosophila transcriptome.

Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to changing environments. We assessed variation in genome-wide gene expression and four fitness-related phenotypes of an outbred Drosophila melanogaster population under 20 different physiological, social, nutritional, chemical, and physical environments; and we compared the phenotypically plastic transcripts to genetically variable transcripts in a single environment. The environmentally sensitive transcriptome consists of two transcript categories, which comprise ∼15% of expressed transcripts. Class I transcripts are genetically variable and associated with detoxification, metabolism, proteolysis, heat shock proteins, and transcriptional regulation. Class II transcripts have low genetic variance and show sexually dimorphic expression enriched for reproductive functions. Clustering analysis of Class I transcripts reveals a fragmented modular organization and distinct environmentally responsive transcriptional signatures for the four fitness-related traits. Our analysis suggests that a restricted environmentally responsive segment of the transcriptome preserves the balance between phenotypic plasticity and environmental canalization.

Iridociliary melanoma with secondary lens luxation: distinctive findings in a long-horned cowfish (Lactoria cornuta).

This report describes a long-horned cowfish, which was diagnosed with buphthalmia and lens sub-luxation in the right eye, conditions that progressed to complete anterior lens luxation and secondary keratoconus. Three months after the initial evaluation, a pigmented mass was observed protruding from the vitreous. An enucleation was performed under general anesthesia. Ocular histopathology revealed an iridociliary melanoma. Reports of intraocular melanomas are extremely rare in fish. To the authors' knowledge, this is the first report of an iridociliary melanoma that led to buphthalmia, lens luxation, and keratoconus in a fish. Histological findings of lens luxation are also demonstrated. Due to the presence of a complex suspensory apparatus involving the teleost lens, this report speculates that lens luxation is a more devastating disease process in teleosts than in mammals.

Prerequisites for implementing cardiovascular absolute risk assessment in general practice: a qualitative study of Australian general practitioners' and patients' views.

BACKGROUND: Although recommended in clinical practice guidelines, cardiovascular absolute risk (CVAR) assessment is still used infrequently in Australian general practice. One reason is the lack of an implementation strategy. Given the lack of published reports on the implementation of CVAR worldwide, the aim of this study was to explore the views of general practitioners (GPs) and patients on prerequisites for successfully implementing CVAR assessment in general practice. METHODS: Multiple data involving GPs and patients were collected using focus groups (FGs) in three divisions of General Practice in Sydney between 2005 and 2006. Both GPs' and patients' opinions were analysed using thematic analysis. RESULTS: Twenty-two GPs participated in three GP FGs and 26 patients in three patient FGs. Many GPs thought that an initial cardiovascular risk screening could start from 40 years old while some patients thought it should start even younger. Targeting patients with known risk factors was supported by most GPs although some also stressed the importance of reaching those of unknown risk. For new patients or patients presenting for other problems, another visit for CVAR risk assessment and discussion was preferred by most GPs. A strong GP-patient relationship, common ground on priorities between GPs and their patients, patient awareness of cardiovascular risk and motivation were seen as important by both GPs and patients to the implementation of CVAR assessment. CONCLUSIONS: Addressing the appropriate selection of patients and time for implementing CVAR assessment requires a consideration of multiple factors. GPs see it as a process that may need to be staged over more than one consultation and requiring appropriate strategies.

Cardiovascular absolute risk assessment and management - engagement and outcomes in general practice patients.

Despite a decline in recent decades, cardiovascular disease (CVD) remains the major cause of death and disability in Australia. To improve primary prevention of CVD, many clinical guidelines recommend using cardiovascular absolute risk (CVAR) assessment to guide risk factor management. Cardiovascular absolute risk assessment predicts the overall risk of a cardiovascular event over a given time period (usually 5 or 10 years). However, use of CVAR is limited and has not been incorporated well in routine general practice. There has been little research on CVAR implementation and an effective implementation strategy has been lacking.

Chronic cor pulmonale secondary to pulmonary atherosclerosis in an African Grey parrot.

CASE DESCRIPTION: A 20-year-old sexually intact female African Grey parrot (Psittacus erithacus) was evaluated to determine the cause of lethargy, hyporexia, weight loss, and persistent ascites of 21 days' duration. CLINICAL FINDINGS: Physical examination revealed a markedly distended abdomen and systolic heart murmur. Thoracic radiography revealed cardiomegaly and hepatomegaly. Doppler echocardiography revealed severe eccentric and concentric hypertrophy of the right ventricle with systolic dysfunction, moderate regurgitation through the right atrioventricular valve, a substantial increase in estimated systolic pulmonary arterial pressure, hepatic venous congestion, and coelomic effusion. A clinical diagnosis of chronic cor pulmonale was established. TREATMENT AND OUTCOME: The parrot was initially stabilized by use of coelomocentesis. During the next month, the parrot was treated by administration of furosemide, hydrochlorothiazide, spironolactone, benazepril, and pimobendan. The parrot appeared to be responding well to treatment but was found dead in its cage 35 days following initial examination. Postmortem examination revealed substantial atherosclerosis of the large pulmonary arteries, with lesions extending into the medium-size arteries. Pulmonary atherosclerosis was suspected as a cause of the severe pulmonary hypertension. CLINICAL RELEVANCE: Although atherosclerosis most commonly affects the systemic and coronary arteries of parrots, sclerotic changes within the pulmonary vasculature should be considered as a possible cause of pulmonary hypertension and as a differential diagnosis for right-sided congestive heart failure in psittacine species.