Non-conventional yeast species for lowering ethanol content of wines

Rising sugar content in grape must, and the concomitant increase in alcohol levels in wine, are some of the main challenges affecting the winemaking industry nowadays. Among the several alternative solutions currently under study, the use of nonconventional yeasts during fermentation holds good promise for contributing to relieve this problem. Non-Saccharomyces wine yeast species comprise a high number or species, so encompassing a wider physiological diversity than Saccharomyces cerevisiae. Indeed, the current oenological interest of these microorganisms was initially triggered by their potential positive contribution to the sensorial complexity of quality wines, through the production of aroma and other sensory-active compounds. This diversity also involves ethanol yield on sugar, one of the most invariant metabolic traits of S. cerevisiae. This review gathers recent research on non-Saccharomyces yeasts, aiming to produce wines with lower alcohol content than those from pure Saccharomyces starters. Critical aspects discussed include the selection of suitable yeast strains (considering there is a noticeable intra-species diversity for ethanol yield, as shown for other fermentation traits), identification of key environmental parameters influencing ethanol yields (including the use of controlled oxygenation conditions), and managing mixed fermentations, by either the sequential or simultaneous inoculation of S. cerevisiae and non-Saccharomyces starter cultures. The feasibility, at the industrial level, of using non-Saccharomyces yeasts for reducing alcohol levels in wine will require an improved understanding of the metabolism of these alternative yeast species, as well as of the interactions between different yeast starters during the fermentation of grape must.Experimental work by researchers from ICVV is supported by the Spanish Government trough MINECO and FEDER funds: MINECO AGL2012-32064 and AGL2015-63629-R grants, INIA RM2012-00007-00-00 grant, MINECO RTC-2014-2186-2 grant, MINECO training contract for AR, MINECO Formación Postdoctoral contract for JC. Experimental work by the authors from Polytechnic University of Marche is supported by Ricerca Scientifica di Ateneo RSA2015.Peer Reviewe

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

Factors affecting the levels of 3-isobutyl-2-methoxypyrazine and C6 compounds in Vitis vinifera L. Merlot.

Two field trials and a regional survey were conducted in Vitis vinifera L.Merlot vineyards located in California over several seasons to investigate the effects of weather variables such as rainfall and growing degree days and vineyard management practices, such as irrigation and fertilization, on the main compounds responsible for fruit and wine green aromas, 3- isobutyl -2 -methoxypyrazine (IBMP) and C 6 compounds. In the first study, the concentration of IBMP and C6 compounds in fruit harvested from 69 commercial vineyards located in three distinctly different wine grape growing regions were measured at commercial maturity from 2007 to 2010. Seasonal variation of green aromas was found to be more important than regional variation, with similar trends among regions observed between for each season. The temperature during the spring, i.e. a period of active vine growth, was found to be the main driver of fruit green aromas at harvest, likely due to interactions with vine vigour and fruit shading. A first field trial was conducted in 2009 and 2010 to investigate the influence of irrigation and N fertilization on green aromas in fruit and wine. Experimental treatments comprised two irrigation levels (the standard irrigation rate of 70% ETc, and 100% of ETc) and a higher than standard nitrogen fertilisation (60 kg/ha, also at 100% of ETc). Irrigation and nitrogen fertilization promoted canopy growth and the decreased fruit exposure resulted in elevated levels of IBMP through fruit maturation compared to the standard irrigation. However, C6 compounds were not affected by either factor. Fruit colour and aroma precursors were higher under deficit irrigation conditions, while vine yield decreased significantly. Wines made with fruit derived from the deficit irrigation treatment were perceived as having less intense vegetal notes, and enhanced fruit characters compared to those from the non deficit treatment. The additional application of nitrogen fertilizer also had a significant and positive effect on the vegetal perception of wines. A second field trial involving exclusion of winter rainfall was also conducted during the 2009 and 2010 growing seasons. Control vines were exposed to normal rainfall conditions, while winter rainfall was excluded from experimental vines by covering the ground with a plastic tarpaulin during the entire dormant season. During the growing season, irrigation in both treatments was maintained at a rate of 70%; of crop evapotranspiration (ETc) until commercial harvest. Canopy growth, berry size and vine yield were significantly reduced on the vines from the rainfall exclusion treatment, and a significant increase in the fruit to pruning weight ratio was recorded over time. IBMP concentration was greater under normal rainfall conditions, and fruit levels remained significantly higher during the season compared to fruit from vines that did not receive winter rainfall. Significantly different concentrations of C6 compounds were only observed in rainfall exclusion fruit towards the end of the second season. Fruit and wine quality parameters, mainly colour and mouth feel compounds, were positively affected by the absence of rainfall in both years. Descriptive analysis indicated that wines from the rainfall exclusion treatment were perceived as being less green and more fruity in the first season. However, as a consequence of the reduction in vine growth, the same treatment produced less fruity wines, of inferior tannin quality in the subsequent season. These findings demonstrate for the first time that vineyard management practices affect fruit and wine IBMP levels, but have no significant impact on the concentration of C6 compounds. As such, grape growers seeking to minimise IBMP fruit levels at harvest would benefit from reduced water and nitrogen application in the vineyard. Furthermore, these results show the importance of achieving adequate canopy growth early in the season, especially under low or no rainfall conditions. Otherwise, the positive effects on fruit and wine quality achieved through reduced berry size may be offset by an even more significant reduction in total yield and a severe lack of balance between vegetative and reproductive growth.Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 201

Seasonal and regional variation of green aroma compounds in commercial vineyards of vitis vinifera L. Merlot in California

A field study was conducted from 2007 to 2010 to examine regional and seasonal variability of the main compounds responsible for green aromas in grapes and wines, 3-isobutyl-2-methoxypyrazine and C6 compounds. Sixty-nine commercial Vitis vinifera L. Merlot vineyards located in three distinctly different winegrape growing regions within the Central Valley of California were sampled at commercial harvest, fruit samples were analyzed for green aroma compounds and standard chemometrics, and several weather parameters such as growing degree days and rainfall were recorded at the vineyard level. Seasonal variation was found to be more important than regional variation, and similar trends among regions were found within each season. Temperature during the spring, a period of active growth, was found to be a significant driver of fruit green aroma compounds at harvest, likely due to its interactions with vine vigor and fruit shading. © 2013 by the American Society for Enology and Viticulture. All rights reserved.Martin P. Mendez-Costabel, Kerry L. Wilkinson, Sue E.P. Bastian, Michael McCarthy, Chris M. Ford, and Nick Dokoozlia

Effect of increased irrigation and additional nitrogen fertilisation on the concentration of green aroma compounds in Vitis vinifera L. Merlot fruit and wine

Article first published online: 9 JAN 2014Background and Aims: Green aroma compounds are considered undesirable when present at a high concentration in red wines. This study aimed to understand the effect of two irrigation levels and a higher than standard nitrogen fertilisation on the concentration of both 3-isobutyl-2-methoxypyrazine (IBMP) and six C6 compounds during fruit development. Methods and Results: Fruit samples were collected biweekly during the 2009 and 2010 seasons in a commercial Vitis vinifera L. Merlot vineyard in California, USA, where two irrigation levels (70 and 100% of crop evapotranspiration) and a higher than standard nitrogen fertilisation dose were implemented. The higher irrigation level and additional nitrogen promoted canopy growth and decreased fruit exposure, resulting in increased concentration of IBMP during fruit maturation. The concentration of the six measured C6 compounds, however, was not affected. Deficit irrigation increased fruit colour, quercetin glycosides and phenol-free glucose glycosides (i.e. aroma precursors), and decreased vine yield. The two irrigation levels did not differ on the sensory vegetal perception of the wines, but the additional application of nitrogen fertiliser at fruitset enhanced it. Significance of the Study: These findings confirm previous work showing that vineyard management practices influence fruit and wine concentration of IBMP, and demonstrate for the first time that the same practices have no significant impact on the concentration of six C6 compounds in grapes or on the concentration of hexanol in wines. Grapegrowers aiming to minimise IBMP concentration in fruit at harvest would probably benefit from a reduced application of water and nitrogen to the vineyard.M.P. Mendez-Costabel, K.L. Wilkinson, S.E.P. Bastian, C. Jordans, M. McCarthy, C.M. Ford and N.K. Dokoozlia