Magnus representation of genome sequences.

We introduce an alignment-free method, the Magnus Representation, to analyze genome sequences. The Magnus Representation captures higher-order information in genome sequences. We combine our approach with the idea of k-mers to define an effectively computable Mean Magnus Vector. We perform phylogenetic analysis on three datasets: mosquito-borne viruses, filoviruses, and bacterial genomes. Our results on ebolaviruses are consistent with previous phylogenetic analyses, and confirm the modern viewpoint that the 2014 West African Ebola outbreak likely originated from Central Africa. Our analysis also confirms the close relationship between Bundibugyo ebolavirus and Taï Forest ebolavirus. For bacterial genomes, our method is able to classify relatively well at the family and genus level, as well as at higher levels such as phylum level. The bacterial genomes are also separated well into Gram-positive and Gram-negative subgroups.

Management and outcomes with 5-year mortality of patients with mildly elevated high-sensitivity troponin T levels not meeting criteria for myocardial infarction.

OBJECTIVES: To examine management and outcomes of patients presenting to EDs with symptoms suggestive of acute coronary syndrome, who have mild non-dynamically elevated high-sensitivity troponin T (HsTnT) levels, not meeting the fourth universal definition of myocardial infarction (MI) criteria (observation group). METHODS: Consecutive patients presenting to the ED with symptoms suggestive of acute coronary syndrome at Liverpool Hospital, Sydney, Australia, those having ≥2 HsTnT levels after initial assessment were adjudicated according to the fourth universal definition of MI, as MI ruled-in, MI ruled-out, or myocardial injury in whom MI is neither ruled-in nor ruled-out (>1 level ≥15 ng/L, called observation group); follow-up was 5 years. RESULTS: Of 2738 patients, 547 were in the observation group, of whom 62% were admitted to hospital, 52% to cardiac services, whereas 97% of MI ruled-in patients and 21% of MI ruled-out patients were admitted; P < 0.001. Non-invasive testing occurred in 42% of observation group patients (36% had echo-cardiography), and 16% had coronary angiography. Of observation group patients, MI rates were 1.5% during hospitalisation and 4% during the following year, similar to that in those with MI ruled-in, among those with MI ruled-out, the MI rate was 0.2%. The 1-year death rate was 13% among observation group patients and 11% MI ruled-in patients (P = 0.624), whereas at 5 years among observation group patients, type 1 MI and type 2 MI were 48%, 26% and 58%, respectively (P = 0.001). CONCLUSION: Very few unselected consecutive patients attending ED, with minor stable HsTnT elevation, had MI, although most had chronic myocardial injury. Late mortality rates among observation group patients were higher than those with confirmed type 1 MI but lower than those with type 2 MI.

Multicultural emergency medicine epidemiology: A health economic analysis of patient visits.

OBJECTIVE: There is growing evidence to suggest that culturally and linguistically diverse (CALD) patients cost the health system more than non-CALD patients because of a higher burden of disease and increased resource consumption. The present study aimed to compare the ED resource utilisation of CALD and non-CALD patients at a tertiary hospital in Sydney, Australia. METHODS: The total ED resource utilisation was calculated by separating each visit into diagnostic test cost and time spent in ED components. The time component was calculated using the product of the total length of stay and a resource cost per unit time measure. Diagnostic tests were costed using the Australian Medicare Benefit Schedule. A generalised additive model was developed to estimate the isolated effect of CALD status on the resource utilisation during an ED visit. RESULTS: CALD patients had a higher median resource utilisation than non-CALD patients ($736.93 vs $701.36, P < 0.0001); however, the generalised additive model demonstrated that CALD status was not independently associated with increased resource utilisation. CONCLUSION: CALD status is not an independent influence on ED resource utilisation but other explanatory variables such as increased age and altered case-mix appear to have a much greater influence. There may, however, be other reasons to consider CALD loading such as equity in healthcare and to address poorer overall health outcomes for CALD patients.

Statistically integrated flow and flood modelling compared to hydrologically integrated quantity and quality model for annual flows in the regulated Macquarie river in arid Australia.

Water resource management traditionally depends on use of highly complex hydrological models designed originally to manage water for abstraction but increasingly relied on to determine ecological impacts and test ecological rehabilitation opportunities. These models are rarely independently tested. We compared a relatively simple statistical model, integrated flow and flood modelling (IFFM), with a complex hydrological model, the integrated quality and quantity model (IQQM), on the highly regulated Macquarie River of the Murray-Darling Basin, southeastern Australia. We compared annual flows (1891-2007) at three gauges to actual data and modelled output: before dams and diversions (unregulated) and after river regulation (regulated), using the goodness of fit (Nash-Sutcliffe coefficient of efficiency) and nonparametric tests. IQQM underestimated impacts of river regulation respectively on median and average flows at the Macquarie Marshes (Oxley gauge) by about 10% and 16%, compared to IFFM. IFFM model output more closely matched actual unregulated and regulated flows than IQQM which tended to underestimate unregulated flows and overestimate regulated flows at the Ramsar-listed wetland. Output was reasonably similar for the two models at the other two flow gauges. Relatively simple statistical models could more reliably estimate ecological impact at floodplains of large river systems, as well as an independent assessment tool compared to complex hydrological models. Finally, such statistical models may be valuable for predicting ecological responses to environmental flows, given their simplicity and relative ease to run.

Lost bed capacity in emergency departments: A descriptive analysis and data visualisation exploration.

OBJECTIVE: To map utilisation of bed resources within an ED over time, in order to determine the proportions of patient stay spent receiving emergency care versus non-emergent care. To produce visualisations that effectively convey this bed utilisation. METHODS: This was a retrospective cohort study using routinely collected administrative data, derived from the ED electronic health record (FirstNet; Cerner, North Kansas City, MO, USA), on all patients presenting to a single tertiary-level ED during a 1-month period and who were triaged to an acute area bed in order to undergo their emergency care. Resuscitation, subacute, fast track and paediatric area patients were excluded from analysis as firstly, in our institution the acute area processing appears to contribute most to barriers to patient flow and secondly, using acute area patients allowed us to approximate standardisation of acuity. Lost bed capacity (LBC) was defined as the time spent in an ED bed after an emergency clinician indicated that they were ready to depart the ED, as recorded in the electronic medical record. RESULTS: The overall proportion of time spent in an ED bed after completion of emergency care was 38.5% (interquartile range 21.8-47.2%). This time differed significantly between 'discharged' (1 min), 'admitted-ward' (72 min) and 'admitted-critical care' (110 min) groups. This was clearly revealed in our novel LBC heatmaps. CONCLUSIONS: A considerable proportion of ED length of stay is because of patients remaining in an ED bed after their emergency care is concluded. Absolute time is much greater for admitted patients than for discharged patients, and therefore efforts to reduce LBC are likely to reduce overall ED length of stay. LBC heatmaps may provide an intuitively useful, potentially automated tool to understand these problems.

Multicultural presentation of chest pain at an emergency department in Australia.

OBJECTIVE: To investigate differences in presenting patient characteristics, investigation, management and related outcomes between culturally and linguistically diverse (CALD) and non-CALD chest pain (CP) patients presenting to the ED. METHODS: A cohort study of 258 patients was enrolled on presentation to Liverpool Hospital ED with a complaint of CP over a 2-week period. Main outcomes included frequency and timeliness of diagnostic and radiological investigations, medication administered and ED length of stay. Administrative and clinical data were extracted and linked from Cerner EMR FirstNet®, PowerChart® and paper records. RESULTS: There were 155 (60%) CALD and 103 (40%) non-CALD patients. CALD patients were older by 10 years (95% CI 4, 15; P < 0.0001). There were no significant differences in the number of pathology and imaging investigations carried out in each group, and similarly there were no significant differences in the number of patients administered analgesia or cardiac-specific medications. Neither group differed in their ED length of stay (median 280 vs 259.5 min; P = 0.79) or hospital admission rate (median 56% vs 55%, P = 0.8). CONCLUSION: Both CALD and non-CALD ED CP patients had similar test ordering, medication administration and clinical outcomes, but this was in the context of CALD patients being 10 years older together with a small study sample size. A larger cohort, matched for age, would provide further insights into potentially important differences.

Lost capacity in emergency departments and its economic implications: A simulation study and economic analysis.

OBJECTIVE: To determine the effect of lost bed capacity (LBC) on the overall capacity of an ED, and to estimate the costs attributable to excess stay in the ED beyond that required for actual emergency care. METHODS: This was a retrospective simulation and health economic evaluation, using data from a single-centre tertiary level ED. Data from all patients who presented to the ED during a 1-month period and triaged to receive an acute bed in order to undergo their emergency care were included. The main outcomes measured were the change in overall ED length of stay, and costs attributable to LBC, in both discharged and admitted patients. RESULTS: Overall daily median ED length of stay decreased by 182 min (95% confidence interval 165-198; P < 0.01) in the simulated cohort when LBC was removed. Within the admitted cohort, the median cost attributable to LBC was AUD$202.99 (95% confidence interval $186.50-$216.70) per patient. We estimate the cost of an ED bed to be AUD$164.59 per hour. CONCLUSIONS: A substantial amount of ED length of stay is due to patients remaining in the ED for time after their emergency care is concluded. This likely represents a substantial overall monetary cost to the Australian healthcare system.

Floretlike cells in in situ and prolapsed orbital fat.

PURPOSE: Orbital pleomorphic lipoma has been rarely reported in the literature. Although floretlike cells are characteristic of pleomorphic lipoma, they are not pathognomonic. We reviewed cases of prolapsed orbital fat and exenteration specimens to determine the significance of presence of these cells in the diagnosis of orbital pleomorphic lipoma. DESIGN: Retrospective interventional case series with clinicopathologic correlation. PARTICIPANTS: Seventy-two specimens of 45 patients with prolapsed orbital fat and 74 exenteration specimens as controls. INTERVENTION: Histologic review of the specimens including light microscopy, Masson trichrome staining, immunostaining for S100, CD34, CD68, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and transmission electron microscopy and review of clinical records and analysis of the data with generalized estimation equation. MAIN OUTCOME MEASURE: Evidence of histologic abnormalities in histologic specimens and clinical and demographic data. RESULTS: Floretlike cells were present in 31 of 72 (43%) specimens of prolapsed orbital fat and in 12 of 74 (16%) orbital exenterations. Fewer than 6 florets were present in twenty 40x high-power fields in 15 (48%), 6 to 10 in 9 (29%), and >10 in 7 (23%) specimens. The florets stained positive for CD34 but not for S100 or CD68. TUNEL assay revealed significant nuclear pyknosis, and transmission electron microscopy disclosed spindle-shaped cells with abundant rough endoplasmic reticulum and no basement membrane. The mean age of patients with prolapsed orbital fat with florets was 67 years (range, 52-86). Of 31 samples, 29 (94%) were from males. Of 30 samples, 29 (97%) were located in the superotemporal conjunctiva; only one was located in the lower lid. There was significant association between the presence of florets and location of the prolapsed orbital fat (P = 0.0013) and gender (P = 0.0015). CONCLUSION: Floretlike cells may be present in in situ and prolapsed orbital fat as a degenerative process. What some have called "orbital pleomorphic lipoma" is in fact only age-related orbital fat prolapse.

Effect of long-term cocaine use on regional left ventricular function as determined by magnetic resonance imaging.

This study examined left ventricular (LV) regional midwall circumferential strain by cardiac tagged magnetic resonance imaging in 32 long-term cocaine users and 14 nonusers. Most of the LV segmentations in the cocaine users had less average circumferential strain in the systolic and diastolic phases. The average diastolic strain in 5 ventricular segmentations was significantly less in the cocaine users (p<0.05). In conclusion, long-term cocaine use may be associated with regional LV dysfunction, especially diastolic dysfunction.

Age, gender and metabolic syndrome-related coronary heart disease in U.S. adults.

BACKGROUND: Metabolic syndrome (MetS), a clustering of several prominent risk factors for atherosclerosis, is common among U.S. populations. The contribution of MetS to the prevalence of coronary heart disease (CHD) in different age-gender groups is currently unknown. METHODS: MetS was defined according to the definition of the National Cholesterol Education Program Adult Treatment Panel III. CHD was defined as having had a diagnosed heart attack in self-reported medical history. Data from the Third National Health and Nutrition Examination Survey (NHANES III) were used to evaluate the MetS-associated CHD prevalences in different age-gender subpopulations, which include 35- to 54-year-old women, 55- to 74-year-old women, 35- to 54-year-old men, and 55- to 74-year-old men. RESULTS: The prevalences of MetS in these 4 age-gender subpopulations are 21%, 24%, 39%, and 38%, respectively. The odds ratios (and the 95% confidence intervals) of MetS to increased CHD in each subpopulations are 1.05 (0.40-2.79), 1.95 (1.19-3.20), 2.22 (1.03-4.81), and 1.96 (1.41-2.70), respectively. CONCLUSIONS: MetS-associated CHD prevalence in women aged 35-54 years is almost the same as in the control, whereas in women aged 55-74 and in men aged 35-54 or 55-74, this prevalence is about 2-fold that of the control. Endogenous estrogen may play a role in suppressing the pro-atherosclerotic effects of MetS-related risk factors, but further studies are needed for a more certain conclusion.

Factors associated with accelerated atherosclerosis in HIV-1-infected persons treated with protease inhibitors.

Recent evidence suggests that as a group protease inhibitors (PIs) may accelerate certain factors associated with atherosclerosis. The objective of this study was to evaluate the effect of individual PIs (indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) on certain factors associated with atherosclerosis. Persons who took saquinavir and/or ritonavir were compared with those on other PIs. Between May 2000 and July 2001, the lipid profiles, C-reactive protein (CRP) levels, coronary artery calcium (CAC) scores, and blood cell morphologic parameters were measured in 98 black adult participants aged 25 to 45 years with HIV-1 infection in Baltimore, Maryland. Among these 98, there were 55 (56.1%) taking PIs. Students' t-test and chi2 test were used to detect the between-group differences. Study participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, red and white blood cell counts, time since HIV diagnosis, and duration on anti-retroviral therapy. Compared with those who took non-PI regimens, those who took indinavir, nelfinavir, or saquinavir had significantly higher levels of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Those taking any PI had significantly higher total cholesterol and low-density lipoprotein. Those taking nelfinavir, ritonavir, or saquinavir were more likely to have a higher CAC score (>5) than those on non-PI regimens. There were no differences in the lipid profiles, MCV, MCH, CRP, and CAC between those taking saquinavir and/or ritonavir and those taking other PIs. Overall, the changes noted might lead to anticipation of clinical changes linked to accelerated atherosclerosis in patients on PIs.

HIV infection and abnormal regional ventricular function.

To examine the effect of HIV infection on regional left ventricular dysfunction in cardiovascularly asymptomatic individuals. Nineteen HIV-negative and 27 HIV-positive cardiovascularly asymptomatic study participants in Baltimore, Maryland were selected and underwent tagged cardiac magnetic resonance imaging. Regional left ventricular myocardial mid-wall peak systolic circumferential strain (Ecc) and early diastolic strain rate (SRE) of the left ventricle were assessed with the use of the harmonic phase analysis. The average Ecc and SRE measurements were compared between HIV-negative and HIV-positive individuals. Compared with the HIV-negatives, the HIV-positives had lower average Ecc and SRE measurements in 90% of the 16 standard left ventricular segments. Of the 14 segments with decreased Ecc strain, 3 were statistically significant and of 14 with decreased strain rate (SRE), 6 were statistically significant. HIV infection may be associated with subclinical regional left ventricular systolic and diastolic dysfunction in individuals free of overt cardiovascular disease.

Early retinal vascular abnormalities in African-American cocaine users.

PURPOSE: To investigate whether cocaine use is associated with early retinal vascular abnormalities. DESIGN: Population-based cross-sectional study. SETTINGS: Inner-city neighborhoods in Baltimore, Maryland. STUDY POPULATION: Sixty-eight participants were recruited from an ongoing observational study, investigating cardiovascular complications of human immunodeficiency virus (HIV) infection and cocaine use in African Americans aged between 25 and 54 years. Those with hypertension and known cardiovascular/cerebrovascular diseases were excluded. OBSERVATION PROCEDURES: Ophthalmoscopic examinations and fundus photography of the retinas of these subjects were performed after pupillary dilation. The largest angle of arterial bifurcation (LAAB), central retinal artery equivalent (CRAE), and central retinal vein equivalent (CRVE) were measured by single-masked fundus image examiners. MAIN OUTCOME MEASURES: LAAB, CRAE, and CRVE. RESULTS: Among the 68 study subjects, 52 (76.5%) were chronic cocaine users and 16 (23.5%) were non-cocaine users. Univariate and multivariate analyses indicated that the LAAB was associated with age and duration of cocaine use of more than 10 years. The LAAB was also inversely associated with very low-density lipoproteins levels. Multivariate analysis indicated a positive association between CRVE and cocaine use. CRAE was also associated with intravenous injection. We confirmed that CRAE was inversely associated with age. HIV infection was not found to be associated with any retinal vascular parameters. CONCLUSIONS: Cocaine use is associated with increased retinal arterial branching angle and venular caliber. The retinal vascular changes provided the first evidence that cocaine use has an effect on the retinal vascular system.

Comparison of central corneal thickness measured by four different pachymeters.

PURPOSE: To compare three different ultrasound pachymeters and an optical scanning device for measuring central corneal thickness (CCT). METHODS: This was a prospective study of 45 consecutive patients (90 eyes), who were seen in consultation for corneal refractive surgery and were tested by the same clinician on one visit. Thirty-five patients with no previous corneal eye surgery (group 1) and 10 who had undergone LASIK (group 2) were analyzed separately. Pachymetry was measured with the Pach V, PachPen, PachMate, and Orbscan II instruments. RESULTS: Generalized Estimation Equations showed significant differences between the Orbscan II and the ultrasound instruments (5.2-22.8 microm) in group 1 and 2, and between the Pach V and the PachPen or PachMate (2.3-3.8 microm) in group 1. In group 2, 10 of 20 eyes had a range of measurements over 20 microns. CONCLUSIONS: In 45 consecutive patients tested on one visit by the same clinician, CCT measured with three ultrasonic pachymeters, including two hand-held units, was clinically comparable in group 2. CCT measured with two ultrasonic pachymeters (i.e., PachMate and PachPen) was clinically comparable in group 1. The Orbscan II data differ from the other three instruments in both groups but more in the patients who had undergone LASIK (group 2).

Intraclass correlation coefficients and bootstrap methods of hierarchical binary outcomes.

Intraclass correlation coefficients are designed to assess consistency or conformity between two or more quantitative measurements. When multistage cluster sampling is implemented, no methods are readily available to estimate intraclass correlations of binomial-distributed outcomes within a cluster. Because statistical distribution of the intraclass correlation coefficients could be complicated or unspecified, we propose using a bootstrap method to estimate the standard error and confidence interval within the framework of a multilevel generalized linear model. We compared the results derived from a parametric bootstrap method with those from a non-parametric bootstrap method and found that the non-parametric method is more robust. For non-parametric bootstrap sampling, we showed that the effectiveness of sampling on the highest level is greater than that on lower levels; to illustrate the effectiveness, we analyse survey data in China and do simulation studies.