A brief visit from a red and extremely elongated interstellar asteroid.

None of the approximately 750,000 known asteroids and comets in the Solar System is thought to have originated outside it, despite models of the formation of planetary systems suggesting that orbital migration of giant planets ejects a large fraction of the original planetesimals into interstellar space. The high predicted number density of icy interstellar objects (2.4 × 10-4 per cubic astronomical unit) suggests that some should have been detected, yet hitherto none has been seen. Many decades of asteroid and comet characterization have yielded formation models that explain the mass distribution, chemical abundances and planetary configuration of the Solar System today, but there has been no way of telling whether the Solar System is typical of planetary systems. Here we report observations and analysis of the object 1I/2017 U1 ('Oumuamua) that demonstrate its extrasolar trajectory, and that thus enable comparisons to be made between material from another planetary system and from our own. Our observations during the brief visit by the object to the inner Solar System reveal it to be asteroidal, with no hint of cometary activity despite an approach within 0.25 astronomical units of the Sun. Spectroscopic measurements show that the surface of the object is spectrally red, consistent with comets or organic-rich asteroids that reside within the Solar System. Light-curve observations indicate that the object has an extremely oblong shape, with a length about ten times its width, and a mean radius of about 102 metres assuming an albedo of 0.04. No known objects in the Solar System have such extreme dimensions. The presence of 'Oumuamua in the Solar System suggests that previous estimates of the number density of interstellar objects, based on the assumption that all such objects were cometary, were pessimistically low. Planned upgrades to contemporary asteroid survey instruments and improved data processing techniques are likely to result in the detection of more interstellar objects in the coming years.

The Proline Variant of the W[F/L/M][T/S]R Cyclic Di-GMP Binding Motif Suppresses Dependence on Signal Association for Regulator Function.

Vibrio vulnificus is an estuarine bacterium and potent opportunistic human pathogen. It enters the food chain by asymptomatically colonizing a variety of marine organisms, most notably oysters. Expression of the brp-encoded extracellular polysaccharide, which enhances cell-surface adherence, is regulated by cyclic di-GMP (c-di-GMP) and the activator BrpT. The Vibrio cholerae and Vibrio parahaemolyticus homologs VpsT and CpsQ, directly bind c-di-GMP via a novel W[F/L/M][T/S]R motif, and c-di-GMP binding is absolutely required for activity. Notably, BrpT belongs to a distinct subclass of VpsT-like regulators that harbor a proline in the third position of the c-di-GMP binding motif (WLPR), and the impact of this change on activity is unknown. We show that the brp locus is organized as two linked operons with BrpT specifically binding to promoters upstream of brpA and brpH Expression data and structural modeling suggested that BrpT might be less dependent on c-di-GMP binding for activity than VpsT or CpsQ. We show that the affinity of BrpT for c-di-GMP is low and that signal binding is not a requisite for BrpT function. Furthermore, a BrpT mutant engineered to carry a canonical WLTR motif (BrpTP124T) bound c-di-GMP with high affinity and its activity was now c-di-GMP dependent. Conversely, introduction of the WLPR motif into VpsT suppressed its dependence on c-di-GMP for activity. This is the first demonstration of reduced dependence on signal association for regulator function within this motif family. Thus, BrpT defines a new class of VpsT-like transcriptional regulators, and the WLPR motif variant may similarly liberate the activity of other subclass members.IMPORTANCE A Vibrio genome may encode nearly 100 proteins that make, break, and bind c-di-GMP, underscoring its central role in the physiology of these bacteria. The activity of the biofilm regulators VpsT of V. cholerae and CpsQ of V. parahaemolyticus is regulated by the direct binding of c-di-GMP via a novel W[F/L/M][T/S]R motif. The V. vulnificus homolog, BrpT, bears an unusual WLPR variant and remains active at low intracellular c-di-GMP levels. This suggests that the WLPR motif may also liberate the activity of other members of this subclass. A single point mutation at the 3rd position of the motif was sufficient to moderate dependence on c-di-GMP binding for activator function, highlighting the simplicity with which complex bacterial signaling networks can be rewired.

Comparing life expectancy and health-adjusted life expectancy by body mass index category in adult Canadians: a descriptive study.

BACKGROUND: While many studies have examined differences between body mass index (BMI) categories in terms of mortality risk and health-related quality of life (HRQL), little is known about the effect of body weight on health expectancy. We examined life expectancy (LE), health-adjusted life expectancy (HALE), and proportion of LE spent in nonoptimal (or poor) health by BMI category for the Canadian adult population (age ≥ 20). METHODS: Respondents to the National Population Health Survey (NPHS) were followed for mortality outcomes from 1994 to 2009. Our study population at baseline (n=12,478) was 20 to 100 years old with an average age of 47. LE was produced by building abridged life tables by sex and BMI category using data from the NPHS and the Canadian Chronic Disease Surveillance System. HALE was estimated using the Health Utilities Index from the Canadian Community Health Survey as a measure of HRQL. The contribution of HRQL to loss of healthy life years for each BMI category was also assessed using two methods: by calculating differences between LE and HALE proportional to LE and by using a decomposition technique to separate out mortality and HRQL contributions to loss of HALE. RESULTS: At age 20, for both sexes, LE is significantly lower in the underweight and obesity class 2+ categories, but significantly higher in the overweight category when compared to normal weight (obesity class 1 was nonsignificant). HALE at age 20 follows these same associations and is significantly lower for class 1 obesity in women. Proportion of life spent in nonoptimal health and decomposition of HALE demonstrate progressively higher losses of healthy life associated with lowered HRQL for BMI categories in excess of normal weight. CONCLUSIONS: Although being in the overweight category for adults may be associated with a gain in life expectancy as compared to normal weight adults, overweight individuals also experience a higher proportion of these years of life in poorer health. Due to the descriptive nature of this study, further research is needed to explore the causal mechanisms which explain these results, including the important differences we observed between sexes and within obesity subcategories.

Surveillance of ischemic heart disease should include physician billing claims: population-based evidence from administrative health data across seven Canadian provinces.

BACKGROUND: Canadian provinces and territories routinely collect health information for administrative purposes. This study used Canadian medical and hospital administrative data for population-based surveillance of diagnosed ischemic heart disease (IHD). METHODS: Hospital discharge abstracts and physician billing claims data from seven provinces were analyzed to estimate prevalence and incidence of IHD using three validated algorithms: a) one hospital discharge abstract with an IHD diagnosis or procedure code (1H); b) 1H or at least three physician claims within a one-year period (1H3P) and c) 1H or at least two physician claims within a one-year period (1H2P). Crude and age-standardized prevalence and incidence rates were calculated for Canadian adults aged 20 +. RESULTS: IHD prevalence and incidence varied by province, were consistently higher among males than females, and increased with age. Prevalence and incidence were lower using the 1H method compared to using the 1H2P or 1H3P methods in all provinces studied for all age groups. For instance, in 2006/07, crude prevalence by province ranged from 3.4%-5.5% (1H), from 4.9%-7.7% (1H3P) and from 6.0%-9.2% (1H2P). Similarly, crude incidence by province ranged from 3.7-5.9 per 1,000 (1H), from 5.0-6.9 per 1,000 (1H3P) and from 6.1-7.9 per 1,000 (1H2P). CONCLUSIONS: Study findings show that incidence and prevalence of diagnosed IHD will be underestimated by as much as 50% using inpatient data alone. The addition of physician claims data are needed to better assess the burden of IHD in Canada.

Diagnosed hypertension in Canada: incidence, prevalence and associated mortality.

BACKGROUND: Hypertension is a leading risk factor for cardiovascular diseases. Our objectives were to examine the prevalence and incidence of diagnosed hypertension in Canada and compare mortality among people with and without diagnosed hypertension. METHODS: We obtained data from linked health administrative databases from each province and territory for adults aged 20 years and older. We used a validated case definition to identify people with hypertension diagnosed between 1998/99 and 2007/08. We excluded pregnant women from the analysis. RESULTS: This retrospective population-based study included more than 26 million people. In 2007/08, about 6 million adults (23.0%) were living with diagnosed hypertension and about 418,000 had a new diagnosis. The age-standardized prevalence increased significantly from 12.5% in 1998/99 to 19.6% in 2007/08, and the incidence decreased from 2.7 to 2.4 per 100. Among people aged 60 years and older, the prevalence was higher among women than among men, as was the incidence among people aged 75 years and older. The prevalence and incidence were highest in the Atlantic region. For all age groups, all-cause mortality was higher among adults with diagnosed hypertension than among those without diagnosed hypertension. INTERPRETATION: The overall prevalence of diagnosed hypertension in Canada from 1998 to 2008 was high and increasing, whereas the incidence declined during the same period. These findings highlight the need to continue monitoring the effectiveness of efforts for managing hypertension and to enhance public health programs aimed at preventing hypertension.

Impact of diabetes mellitus on life expectancy and health-adjusted life expectancy in Canada.

The objectives of this study were to estimate life expectancy (LE) and health-adjusted life expectancy (HALE) for Canadians with and without diabetes and to evaluate the impact of diabetes on population health using administrative and survey data.Mortality data from the Canadian Chronic Disease Surveillance System (2004 to 2006) and Health Utilities Index data from the Canadian Community Health Survey (2000 to 2005) were used. Life table analysis was applied to calculate LE, HALE, and their confidence intervals using the Chiang and the adapted Sullivan methods.LE and HALE were significantly lower among people with diabetes than for people without the disease. LE and HALE for females without diabetes were 85.0 and 73.3 years, respectively (males: 80.2 and 70.9 years). Diabetes was associated with a loss of LE and HALE of 6.0 years and 5.8 years, respectively, for females, and 5.0 years and 5.3 years, respectively, for males, living with diabetes at 55 years of age. The overall gains in LE and HALE after the hypothetical elimination of prevalent diagnosed diabetes cases in the population were 1.4 years and 1.2 years, respectively, for females, and 1.3 years for both LE and HALE for males.The results of the study confirm that diabetes is an important disease burden in Canada impacting the female and male populations differently. The methods can be used to calculate LE and HALE for other chronic conditions, providing useful information for public health researchers and policymakers.

The Campylobacter jejuni Response Regulator and Cyclic-Di-GMP Binding CbrR Is a Novel Regulator of Flagellar Motility.

A leading cause of bacterial gastroenteritis, Campylobacter jejuni is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a C. jejuni response regulator that is annotated as a diguanylate cyclase (DGC), an enzyme that catalyzes the synthesis of c-di-GMP, a universal bacterial second messenger, from GTP. In C. jejuni DRH212, we constructed an unmarked deletion mutant, cbrR-, and complemented mutant, cbrR+. Motility assays indicated a hyper-motile phenotype associated with cbrR-, whereas motility was deficient in cbrR+. The overexpression of CbrR in cbrR+ was accompanied by a reduction in expression of FlaA, the major flagellin. Biofilm assays and scanning electron microscopy demonstrated similarities between DRH212 and cbrR-; however, cbrR+ was unable to form significant biofilms. Transmission electron microscopy showed similar cell morphology between the three strains; however, cbrR+ cells lacked flagella. Differential radial capillary action of ligand assays (DRaCALA) showed that CbrR binds GTP and c-di-GMP. Liquid chromatography tandem mass spectrometry detected low levels of c-di-GMP in C. jejuni and in E. coli expressing CbrR. CbrR is therefore a negative regulator of FlaA expression and motility, a critical virulence factor in C. jejuni pathogenesis.

Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in Vibrio vulnificus.

Poor clinical outcomes (disfigurement, amputation, and death) and significant economic losses in the aquaculture industry can be attributed to the potent opportunistic human pathogen Vibrio vulnificusV. vulnificus, as well as the bivalves (oysters) it naturally colonizes, is indigenous to estuaries and human-inhabited coastal regions and must endure constantly changing environmental conditions as freshwater and seawater enter, mix, and exit the water column. Elevated cellular c-di-GMP levels trigger biofilm formation, but relatively little is known regarding the environmental signals that initiate this response. Here, we show that calcium is a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers expression of the brp extracellular polysaccharide that enhances biofilm formation. A transposon screen for the loss of calcium-induced PbrpA expression revealed CysD, an enzyme in the sulfate assimilation pathway. Targeted disruption of the pathway indicated that the production of a specific metabolic intermediate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), was required for calcium-induced PbrpA expression and that PAPS was separately required for development of the physiologically distinct rugose phenotype. Thus, PAPS behaves as a second messenger in V. vulnificus Moreover, c-di-GMP and BrpT (the activator of brp expression) acted in concert to bias expression of the sulfate assimilation pathway toward PAPS and c-di-GMP accumulation, establishing a feed-forward regulatory loop to boost brp expression. Thus, this signaling network links extracellular calcium and sulfur availability to the intracellular second messengers PAPS and c-di-GMP in the regulation of V. vulnificus biofilm formation and rugosity, survival phenotypes underpinning its evolution as a resilient environmental organism.IMPORTANCE The second messenger c-di-GMP is a key regulator of bacterial physiology. The V. vulnificus genome encodes nearly 100 proteins predicted to make, break, and bind c-di-GMP. However, relatively little is known regarding the environmental signals that regulate c-di-GMP levels and biofilm formation in V. vulnificus Here, we identify calcium as a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers brp-mediated biofilm formation. We show that PAPS, a metabolic intermediate of the sulfate assimilation pathway, acts as a second messenger linking environmental calcium and sulfur source availability to the production of another intracellular second messenger (c-di-GMP) to regulate biofilm and rugose colony formation, developmental pathways that are associated with environmental persistence and efficient bivalve colonization by this potent human pathogen.

Assessing the burden of hospitalized and community-care heart failure in Canada.

BACKGROUND: The surveillance of heart failure (HF) is currently conducted using either survey or hospital data, which have many limitations. Because Canada is collecting medical information in administrative health data, the present study seeks to propose methods for the national surveillance of HF using linked population-based data. METHODS: Linked administrative data from 5 Canadian provinces were analyzed to estimate prevalence, incidence, and mortality rates for persons with HF between 1996/1997 and 2008/2009 using 2 case definitions: (1) 1 hospitalization with an HF diagnosis in any field (H_Any) and (2) 1 hospitalization in any field or at least 2 physician claims within a 1-year period (H_Any_2P). One hospitalization with an HF diagnosis code in the most responsible diagnosis field (H_MR) was also compared. Rates were calculated for individuals aged ≥ 40 years. RESULTS: In 2008/2009, combining the 5 provinces (approximately 82% of Canada's total population), both age-standardized HF prevalence and incidence were underestimated by 39% and 33%, respectively, with H_Any when compared with H_Any_2P. Mortality was higher in patients with H_MR compared with H_Any. The degree of underestimation varied by province and by age, with older age groups presenting the largest differences. Prevalence estimates were stable over the years, especially for the H_Any_2P case definition. CONCLUSIONS: The prevalence and incidence of HF using inpatient data alone likely underestimates the population rates by at least 33%. The addition of physician claims data is likely to provide a more inclusive estimate of the burden of HF in Canada.

Health-Adjusted Life Expectancy among Canadian Adults with and without Hypertension.

Hypertension can lead to cardiovascular diseases and other chronic conditions. While the impact of hypertension on premature death and life expectancy has been published, the impact on health-adjusted life expectancy has not, and constitutes the research objective of this study. Health-adjusted life expectancy (HALE) is the number of expected years of life equivalent to years lived in full health. Data were obtained from the Canadian Chronic Disease Surveillance System (mortality data 2004-2006) and the Canadian Community Health Survey (Health Utilities Index data 2000-2005) for people with and without hypertension. Life table analysis was applied to calculate life expectancy and health-adjusted life expectancy and their confidence intervals. Our results show that for Canadians 20 years of age, without hypertension, life expectancy is 65.4 years and 61.0 years, for females and males, respectively. HALE is 55.0 years and 52.8 years for the two sexes at age 20; and 24.7 years and 22.9 years at age 55. For Canadians with hypertension, HALE is only 48.9 years and 47.1 years for the two sexes at age 20; and 22.7 years and 20.2 years at age 55. Hypertension is associated with a significant loss in health-adjusted life expectancy compared to life expectancy.

Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase.

Sphingosine 1-phosphate (S1P) rapidly increases endothelial barrier function and induces the assembly of the adherens junction proteins vascular endothelial (VE)-cadherin and catenins. Since VE-cadherin contributes to the stabilization of the endothelial barrier, we determined whether the rapid, barrier-enhancing activity of S1P requires VE-cadherin. Ca(2+)-dependent, homophilic VE-cadherin binding of endothelial cells, derived from human umbilical veins and grown as monolayers, was disrupted with EGTA, an antibody to the extracellular domain of VE-cadherin, or gene silencing of VE-cadherin with small interfering RNA. All three protocols caused a reduction in the immunofluorescent localization of VE-cadherin at intercellular junctions, the separation of adjacent cells, and a decrease in basal endothelial electrical resistance. In all three conditions, S1P rapidly increased endothelial electrical resistance. These findings demonstrate that S1P enhances the endothelial barrier independently of homophilic VE-cadherin binding. Junctional localization of VE-cadherin, however, was associated with the sustained activity of S1P. Imaging with phase-contrast and differential interference contrast optics revealed that S1P induced cell spreading and closure of intercellular gaps. Pretreatment with latrunculin B, an inhibitor of actin polymerization, or Y-27632, a Rho kinase inhibitor, attenuated cell spreading and the rapid increase in electrical resistance induced by S1P. We conclude that S1P rapidly closes intercellular gaps, resulting in an increased electrical resistance across endothelial cell monolayers, via cell spreading and Rho kinase and independently of VE-cadherin.

The burden of adult obesity in Canada.

Obesity is a major public health problem associated with a wide range of health problems. This study estimates the prevalence of obesity, calculates the proportion (or population-attributable fraction [PAF]) of major chronic diseases which is attributable to obesity, estimates the deaths attributable to it and projects its future prevalence trends. In Canada, the overall age-standardized prevalence proportion of obesity has increased from 10 percent in 1970 to 23% in 2004 (8 percent to 23 percent in men and 13 percent to 22 percent in women). The increasing prevalence of obesity was observed for all five age groups examined: 20-34, 35-44, 45-54, 55-64 and 65+. On average, the PAF of prevalence of selected major chronic diseases which is attributable to obesity from 1970 to 2004 has increased by 138 percent for men and by 60 percent for women. Overall, in 2004, 45 percent of hypertension, 39 percent of type II diabetes, 35 percent of gallbladder disease, 23 percent of coronary artery diseases (CAD), 19 percent of osteoarthritis, 11 percent of stroke, 22 percent of endometrial cancer, 12 percent of postmenopausal breast cancer, and 10 percent of colon cancer could be attributed to obesity. In 2004, 8,414 (95 percent CI: 6,881-9,927) deaths were attributable to obesity. If current obesity prevalence trends remain unchanged, the prevalence proportion of obesity in Canada is projected to reach 27 percent in men and 24 percent in women by the year 2010. These increases will have a profound impact on the treatment needs and prevalence of a wide variety of chronic diseases, and also on the health care system in terms of capacity issues and resource allocation.

Trends in mortality from ischemic heart disease in Canada, 1986-2000.

This study examined trends in ischemic heart disease (IHD) mortality rates in Canada from 1986 to 2000, including analyses at the county level. The study population comprised Canadians aged 35 and over. Age-standardized mortality rates (ASMRs) were computed. Linear regression and Poisson regression were used to calculate average annual percentage change (AAPC) by age, sex, county and province. A substantial decrease in mortality rates was observed in those aged 35 and over for both sexes; the AAPC indicated a decline of 3.44 percent for males and 3.42 percent for females. The ASMRs were plotted for three time periods; the rates increased with each successive age group and decreased with each consecutive time period for both sexes. A significant decline in the IHD mortality rate was found in 47.2 percent and 46.9 percent of the counties among males and females, respectively; those counties had a statistically significant lower prevalence of daily smoking in both genders, and obese in females only. Only two counties showed a significant increase in the ASMRs of IHD in males and females, respectively. Enhanced prevention and control strategies should be considered to address IHD in countries where more modest decreases (or no decrease at all) in IHD mortality have been observed.

Trends in mortality from diabetes mellitus in Canada, 1986-2000.

The purpose of this study was to examine trends in diabetes mellitus (DM) mortality rates in Canada, including analysis at the provincial level, during the period 1986-2000. The study population included Canadians aged 35 and over. Age-standardized mortality rates (ASMRs) were computed. Linear regression was used to calculate the average annual percentage change (AAPC) by age, sex and province. The results showed a substantial increase in DM mortality rates among those aged 35 and over, particularly for men; the AAPC indicated an increase of 2.4% for men and 0.7% for women. When the mortality rates were plotted for three time periods, the rates increased with each successive age group and period for both sexes. Mortality from DM increased significantly in both sexes in Canada between 1986 and 2000, particularly in men.

Prostate cancer--testing, incidence, surgery and mortality.

OBJECTIVES: This article examines recent use of the prostate-specific antigen (PSA) test and presents trends in prostate cancer incidence, surgery and mortality. DATA SOURCES: Data are from the 2000/01 Canadian Community Health Survey, the National Cancer Incidence Reporting System and the Canadian Cancer Registry, the Hospital Morbidity Database, and the Canadian Mortality Database. ANALYTICAL TECHNIQUES: Descriptive data on PSA testing among men aged 40 or older were produced. Age-standardized prostate cancer incidence, surgery and mortality rates were calculated. Significant changes in linear trends were detected with joinpoint analysis. Provincial differences in incidence and mortality rates were tested using a one-way analysis of variance (ANOVA). MAIN RESULTS: In 2000/01, 43% of Canadian men aged 40 or older reported having had a PSA test. Prostate cancer incidence rates rose in the early 1990s, but have since fallen. Prostate cancer mortality rates have decreased among men aged 60 or older, but show little change among younger men. While interprovincial differences in rates of PSA testing were significant, differences in incidence and mortality rates were not pronounced.

Rapid detection and identification of human adenovirus species by adenoplex, a multiplex PCR-enzyme hybridization assay.

Human adenoviruses (AdV) have been implicated in a wide variety of diseases and are ubiquitous in populations worldwide. These agents are of concern particularly in immunocompromised patients, children, and military recruits, resulting in severe disease or death. Clinical diagnosis of AdV is usually achieved through routine viral cell culture, which can take weeks for results. Immunofluorescence and enzyme-linked immunosorbent assay-based techniques are more timely but lack sensitivity. The ability to distinguish between the six different AdV species (A to F) is diagnostically relevant, as infections with specific AdV species are often associated with unique clinical outcomes and epidemiological features. Therefore, we developed a multiplex PCR-enzyme hybridization assay, the Adenoplex, using primers to the fiber gene that can simultaneously detect all six AdV species A through F in a single test. The limit of detection (LOD) based on the viral 50% tissue culture infective dose/ml for AdV A, B, C, D, E, and F was 10(-2), 10(-1), 10(-1), 10(-2), 10(-1), and 10(-2), respectively. Similarly, the LOD for the six DNA controls ranged from 10(2) to 10(3) copies/ml. Twelve common respiratory pathogens were tested with the Adenoplex, and no cross-reactivity was observed. We also validated our assay using clinical specimens spiked with different concentrations of AdV strains of each species type and tested by multiplex PCR and culture. The results demonstrated an overall sensitivity and specificity of Adenoplex of 100%. This assay can be completed in as few as 5 h and provides a rapid, specific, and sensitive method to detect and subtype AdV species A through F.