Hypotaurine and thiotaurine as indicators of sulfide exposure in bivalves and vestimentiferans from hydrothermal vents and cold seeps

Author Posting. © Blackwell, 2007. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Marine Ecology 28 (2007): 208-218, doi:10.1111/j.1439-0485.2006.00113.x.Vesicomyid clams, vestimentiferans, and some bathymodiolin mussels from hydrothermal vents and cold seeps possess thiotrophic endosymbionts, high levels of hypotaurine and, in tissues with symbionts, thiotaurine. The latter, a product of hypotaurine and sulfide, may store and/or transport sulfide non-toxically, and the ratio to hypotaurine plus thiotaurine (Th/[H+Th]) may reflect an animal's sulfide exposure. To test this, we analyzed seep and vent animals with in situ sulfide measurements. Calyptogena kilmeri clams occur at high-sulfide seeps in Monterey Canyon, while C. (Vesicomya) pacifica clams occur at seeps with lower levels but take up and metabolize sulfide more effectively. From one seep where they co-occur, both had gill thiotaurine contents at 22-25 mmol/kg wet mass, and while C. (V.) pacifica had a higher blood sulfide level, it had a lower Th/[H+Th] (0.39) than C. kilmeri (0.63). However, these same species from different seeps with lower sulfide exposures had lower ratios. Bathymodiolus thermophilus (East Pacific Rise [EPR 9°50'N]) from high- (84 μM) and a low- (7 μM) sulfide vents had gill ratios of 0.40 and 0.12, respectively. Trophosomes of Riftia pachyptila (EPR 9°50'N) from medium- (33 μM) and low- (4 μM) sulfide vents had ratios of 0.23 and 0.20, respectively (not significantly different). Ridgeia piscesae vestimentiferans (Juan de Fuca Ridge) have very different phenotypes at high- and low-sulfide sites, and their trophosomes had the greatest differences: 0.81 and 0.04 ratios from high- and low-sulfide sites, respectively. Thus Th/[H+Th] may indicate sulfide exposure levels within species, but not in interspecies comparisons, possibly due to phylogenetic and metabolic differences. Total H+Th was constant within each species (except in R. piscesae); the sum may indicate the maximum potential sulfide load that a species faces.Funding for Ridgeia piscesae collection was grant UAF01-0042 from NOAA-West Coast National Undersea Research Center to Stephen W. Schaeffer, Charles R. Fisher, and Stéphane Hourdez. Funding for GLB, RVH and PHY was the W.M. Keck Foundation (grant to Whitman College Life Sciences program) and Whitman College Perry Grant program. Funding was from Ifremer for NLB, and The David and Lucile Packard Foundation for SKG

Acaricide resistance profiles of single- and multi-host ticks from communal and commercial farming areas in the Eastern Cape and North-West Provinces of South Africa

A field study (February 2000 to August 2001) was conducted on communal and commercial farms in the Eastern Cape and North-West Provinces of South Africa to detect the levels of tick resistance to commonly used acaricides. The larvae obtained from engorged females of the one-host tick Boophilus decoloratus, the two-host tick Rhipicepalus evertsi evertsi and the three-host ticks Amblyomma hebraeum and Rhipicephalus appendiculatus were tested against various concentrations of amitraz , chlorfenvinphos and cypermethrin using the Shaw Larval Immersion Test method. Ticks from the communal farms showed higher levels of resistance to cypermethrin and some resistance to chlorfenvinphos whilst no resistance was detected against amitraz. However, ticks from commercial farms were equally resistant to amitraz, chlorfenvinphos and cypermethrin. The B. decoloratus populations tested were considerably more resistant to all the acaricides tested than the R. evertsi evertsi, A. hebraeum and R. appendiculatus populations. This supports the hypothesis that single-host ticks develop resistance faster than multi-host ticks. This trend was recorded on most of the farms where single- and multi-host ticks co-existed. It was concluded that the use of acaricides at high frequencies and high concentrations was one of the main causes of tick resistance in the study areas. Possible factors which caused the resistance problems are discussed and acaricide management strategies recommended.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat v.9 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The Association of Pediatric Critical Care Medicine Training Programs with Research Publication Productivity and Employment Outcomes of Their Graduates

Our objective was to associate characteristics of pediatric critical care medicine (PCCM) fellowship training programs with career outcomes of PCCM physicians, including research publication productivity and employment characteristics. This is a descriptive study using publicly available data from 2557 PCCM physicians from the National Provider Index registry. We analyzed data on a systematic sample of 690 PCCM physicians representing 62 fellowship programs. There was substantial diversity in the characteristics of fellowship training programs in terms of fellowship size, intensive care unit (ICU) bed numbers, age of program, location, research rank of affiliated medical school, and academic metrics based on publication productivity of their graduates standardized over time. The clinical and academic attributes of fellowship training programs were associated with publication success and characteristics of their graduates\u27 employment hospital. Programs with greater publication rate per graduate had more ICU beds and were associated with higher ranked medical schools. At the physician level, training program attributes including larger size, older program, and higher academic metrics were associated with graduates with greater publication productivity. There were varied characteristics of current employment hospitals, with graduates from larger, more academic fellowship training programs more likely to work in larger pediatric intensive care units (24 [interquartile range, IQR: 16-35] vs. 19 [IQR: 12-24] beds;  \u3c 0.001), freestanding children\u27s hospitals (52.6 vs. 26.3%;  \u3c 0.001), hospitals with fellowship programs (57.3 vs. 40.3%;  = 0.01), and higher affiliated medical school research ranks (35.5 [IQR: 14-72] vs. 62 [IQR: 32, unranked];  \u3c 0.001). Large programs with higher academic metrics train physicians with greater publication success (H index 3 [IQR: 1-7] vs. 2 [IQR: 0-6];  \u3c 0.001) and greater likelihood of working in large academic centers. These associations may guide prospective trainees as they choose training programs that may foster their career values

Effects of nasal corticosteroids on boosts of systemic allergen-specific IgE production induced by nasal allergen exposure.

Allergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear.Here we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure.Subjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1-4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter.Nasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects.In conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure.http://clinicaltrials.gov/NCT00755066