dataesr/scientific-paragraphs-categorization huggingface dataset:
4% for allcause mortality. An advantage of our analyses is that they reflect the use of VKAs in real life, where VKA treatment in patients with AF usually is not initiated with overlapping treatment with heparin to overcome the prothrombotic activity of VKA in the initial treatment period. Putting these results into perspective, it is apparent from the literature that optimisation of VKA control has not improved over time. Hylek et al. [15]  analysed the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic AF and stated that tight control of anticoagulant therapy to maintain the INR between 2. 0 and 3. 0 is a better strategy than targeting lower, less effective levels of anticoagulation. More recently, Gallagher et al. [16]  in a retrospective study of the medical records from 37,907 patients with AF from the UK General Practice Research Database found that TTR was a strong predictor of stroke.
This work was supported by an educational research grant from  Bayer Pharma AG, Berlin, Germany  (http://pharma. bayer. com) to the  Thrombosis Research Institute, London ,  AF registry. The funding source had no involvement in the data collection, data analysis, or data interpretation. Leo, and  Roche ; consultant for Stago and Philips; research funding from  Bayer ,  Boehringer Ingelheim , and  AstraZeneca ; and Chair of boardadvisory board for Bayer. SZG: research funding from  BiO2 Medical, Boehringer-Ingelheim ,  Bristol Meyers Squibb ,  BTG EKOS ,  Daiichi Sankyo ,  National Heart Lung and Blood Institute of the National Institutes of Health ,  Janssen , and Thrombosis Research Group; and consultant for  Bayer, Boehringer-Ingelheim ,  Bristol Meyers Squibb ,  Daiichi Sankyo ,  Janssen , and Portola.
Acknowledgments This review was presented as an oral communication at the Keele Meeting in Lille (February-March 2015). Many thanks to  Mrs. Lechat  for secretarial assistance. We also thank all surgeons or clinicians who addressed bone samples to our laboratory and especially  D. Moukoko ,  N. Henric ,  V. Steiger ,  P. Le Nay ,  J. M. Frin ,  C. De Bodman ,  D. Mulleman ,  M. Audran ,  E. Legrand ,  B. Bouvard. This research was funded by the  Ministère de l'Enseignement Supérieur et de la Recherche.
Nevertheless, the Cd 2+ -dependent inhibition of the BLM unwinding activity was not reversed by EDTA, suggesting an additional catalytic mechanism of inhibition, unrelated to the DNA-binding step. According to the three-dimensional BLM structure  51, 52  , we performed single point mutations of Cys residues implicated in DNA binding/unwinding (C895S and C901S). The two BLM mutants displayed modest reduced DNA-unwinding activity and their responses to Cd 2+ were similar to the wild-type BLM (data not shown). This suggests that distinct residues (Cys or other amino-acids) or, alternatively, a combination of the two above-mentioned Cys could be responsible for the irreversible BLM inactivation by Cd 2+. The underlying mechanism is currently under investigation.
Acknowledgements This work was supported by the  National Natural Science Foundation of China  (no. 31370798 ,  11304252  and  31301632 ), the 985 and 211 Projects from the  Ministry of Education of China  and the  Centre National de la Recherche Scientifique. N. B. was supported by fellowships from  la Ligue contre le Cancer  and the  Association pour la Recherche sur le Cancer. This research was also partially funded by the  CNRS LIA  ("Helicase-mediated G-quadruplex DNA unwinding and genome stability").
¶ Note that data shown in Fig. 2  and 3  are representative from a series of measurements performed under slightly different conditions, but for which the very same trends were observed. (inset in Fig. 1 ). The rate of 7-OH-CCA formation is dependent on the Cu(Aβ 16 ) concentration. This is in line with the slower rate of HO • formation in the presence of Aβ 16. The same trends were observed for the longer peptide encompassing the first 28 amino-acid residues and the full-length peptide (Fig. S10 † ). Finally, the total amounts of 7-OH-CCA produced were measured. For doing this, the reaction was stopped after the total consumption of ascorbate (arrows in Fig. 1 ), and the intensities of the plateau were compared (Fig. 3 ) as a function of the initial ascorbate concentration and the Cu (resp.
Acknowledgments The authors acknowledge  L. Debrauwer  and  E. Jamin  for providing the Orbitrap mass spectrometer (MetaToul-AXIOM,  INRA ,  UMR1331  Toxalim, Toulouse, France). F. C. and P. F. thank the  ANR -ANR-13-BSV5-0016 ; C. H. thanks the  ERC aLzINK  -contract no. 638712  for financial support.
Included Studies ] [8]  Study NCT00081458 (ClinicalTrials. gov identifier; EudraCT, 2004-000438-35) and STEPS (NCT00798967; EudraCT, 2008-006193-15) were 24-week, double-blind RCTs of subcutaneous teduglutide (0. 05 or 0. 10 mg/kg/d in NCT00081458 and 0. 05 mg/ kg/d in STEPS). 3, 5 Study NCT00172185 was a double-blind, 28-week extension of NCT00081458. 7 In study NCT00172185, patients who received teduglutide in NCT00081458 continued on the same teduglutide dose in the extension study, and patients who received placebo were randomized 1:1 to treatment with subcutaneous teduglutide 0. 05 or 0. 10 mg/kg/d. Total treatment time for patients who received teduglutide in NCT00081458 and completed the NCT00172185 extension was 1 year. STEPS-2 (NCT00930644; EudraCT, 2009-011679-65) was a 2-year, openlabel extension of the phase III STEPS RCT.
8  Patients were eligible to enroll in STEPS-2 if they had completed either the placebo or teduglutide arm of STEPS. In addition, patients who completed the fluid optimization and stabilization phase in STEPS but were not randomized to treatment because of full study enrollment could be enrolled directly into STEPS-2. All patients received subcutaneous teduglutide 0. 05 mg/kg/d. STEPS-3 (NCT01560403) was a 1-year open-label extension of STEPS-2; total treatment time for patients who received teduglutide in STEPS and completed STEPS-2 and STEPS-3 was 42 months. 6 Full eligibility criteria for these studies have been published previously. 3, 5, 7 ll studies were conducted in compliance with International Conference on Harmonisation Good Clinical Practice guidelines and the World Medical Association Declaration of Helsinki and its amendments.
Protocol for Parenteral Support Optimization and Adjustments Before randomization in the placebo-controlled studies, fluid balance was optimized and stabilized for up to 16 weeks using a standardized protocol to ensure adequate hydration status and urine output (target: 1-2 L/d) across all patients and clinical sites. 3, 5 Baseline values for PS requirements were determined following completion of the optimization/stabilization phases for all patients and at the start of teduglutide treatment (at the time of randomization for patients who received teduglutide in study NCT00081458 or STEPS and at the time of enrollment into the extension studies for all other patients). In all studies, patients were managed according to an algorithm that permitted PS reductions of 10%-30% of baseline volume if clinical status was stable and 48-hour urine output had increased by ≥10% over baseline.
End Points and Statistical Analysis This post hoc analysis of pooled data evaluated the percentage of patients who achieved independence from PS during treatment with teduglutide 0. 05 mg/kg/d, the dose approved by the U. S. Food and Drug Administration and the European Medicines Agency. 10, 11 Treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) for patients who achieved independence from PS were coded using the Medical Dictionary for Regulatory Activities. A χ 2 test and Fisher exact test were used to analyze the frequency of PS independence in patients who maintained colon-in-continuity and those who did not. All other end-point analyses were performed using descriptive statistics. No additional between-group comparisons or correlations were performed in this patient population because of the nature of the extension studies and small patient numbers.
5 years in long-term clinical studies,  [6] [7] [8]  the PS independence data also suggest that teduglutide is associated with PS benefits accrued over time; thus, regular monitoring as part of individualized patient management is recommended. The adult patients with SBS who enrolled in the phase III teduglutide studies had a wide range of underlying disease characteristics, including varying remnant bowel anatomy. The prognostic factors previously associated with spontaneous adaptation, such as remnant bowel length or colon-in-continuity, did not clearly predict teduglutide-induced enteral autonomy in this study. 12, 13 The remaining small intestine length ranged from 26-250 cm. Although most patients who achieved  independence from PS had colon-in-continuity (12/16), χ 2 and Fisher exact tests did not show a significant association between the presence or absence of colon-in-continuity and PS weaning, perhaps because of small patient numbers.
Patients in these studies achieved oral or enteral autonomy despite a relatively high incidence of TEAEs and TESAEs, suggesting that AEs can be managed to achieve optimal results with teduglutide. This cohort of patients who obtained oral or enteral autonomy while receiving teduglutide all continued teduglutide treatment past the point of PS weaning until the end of the clinical study period. This pooled clinical trial post hoc analysis was unable to add to the limited available data regarding outcomes of patients who discontinue teduglutide. However, 3 patients in this cohort who participated in the NCT00081458 and NCT00172185 studies were included in the Compher et al  14  post hoc analysis that reported that all remained independent of PS 12 months after withdrawal of 0. 05 mg/kg/d teduglutide.
5 L/wk between end of treatment and the 4-week follow-up visit. 7 hese findings highlight the importance of individualized patient management with teduglutide and continued monitoring after PS weaning. Patients who obtain oral or enteral autonomy still have their underlying condition of SBS and will likely continue to require specialized diets, vitamin and other micronutrient supplementation, concomitant antidiarrheal and other medications, and fluid optimization after weaning. 15 his study was limited by the small patient sample size, which precluded performance of regression analyses for predictive factors associated with PS independence. In addition, the studies pooled for this analysis included minor protocol differences that may have influenced rates of PS weaning. For example, the weaning algorithm in NCT00081458/ NCT00172185 permitted a 10% maximum reduction from baseline in PS volume during a PS adjustment vs a 30% maximum reduction in the STEPS study and its extension.
3, 5, 7, 8 The intervals between study visits were also shorter in the RCTs compared with the extension studies (2-4 vs 2-12 weeks, respectively). Furthermore, the influence of spontaneous intestinal adaptation on PS weaning during the extension studies is currently unclear. Although most spontaneous intestinal adaptation is thought to occur during the first 2 years following small bowel resection, recent studies indicate that adaptation can advance over longer time periods. 12, 16 Finally, the patients described here were managed under strict clinical trial protocols and may not fully reflect the experiences of patients treated in general clinical practice. The ongoing teduglutide global registration study (ClinicalTrials. gov identifier: NCT01990040) will provide critical data regarding the efficacy and safety of teduglutide treatment under real-world conditions.
An elevated consumption of drinking water was also associated with higher levels of physical activity  [22, 23]. However, in France, there is a paucity of studies describing drinking water patterns in light of socio-demographic determinants and a complete lack of research on the association between drinking water intake and diet quality. Based on data from a representative sample of the French adult population, the present study examined if there was an association between drinking water intake and diet quality assessed by several dietary indices. We hypothesised that the largest drinking water consumers had a better diet quality. We also estimated the adherence of men and women to the AI proposed by the EFSA and analysed the contributions of the different TWI sources.
Study Population The second Individual and National Food Consumption Survey (INCA2) was carried out by ANSES (the French Agency for Food, Environmental, and Occupational Health) between December 2005 and May 2007 among representative samples of French adults and children to collect information on habitual food and beverage consumption. The samples were obtained using a multi-stage cluster sampling technique, established by the National Institute for Statistics and Economic Studies (INSEE). The sampling frame was approved by the French National Commission for Computed Data and Individual Freedom (Commission Nationale de l'Informatique et des Libertés, CNIL). The present analyses used data from the adult sample of the INCA2 (n = 1918) including men (n = 776) and women (n = 1142) aged 18-79 years old.
Dietary Assessment Diet was assessed using a seven-day open-ended food record. Each day of the food record was divided into three main meals (breakfast, lunch, and dinner) and three between-meals snacks. The individuals were asked to describe, as precisely as possible, all food and beverage intakes for seven consecutive days: food name, origin (home-made or industrial product), and features (low fat, low sugar, fortified, dietetic, as well as fresh, canned, or frozen). Portion sizes were expressed by weight or household measures (spoon) or estimated using a photographic booklet (SU. VI. MAX)  [30]. Average daily nutritional intakes (excluding all alcoholic beverages) were evaluated matching food intakes with the 2013 French food composition database of the CIQUAL led by ANSES  [31]. Daily TWI, expressed in grams per day, was estimated by assessing the amount of the nutrient "water", from fluids and from food moisture.
Diet Cost Diet cost was calculated by multiplying the quantity of each food in the diet by its mean national price. A detailed methodology has been previously described  [39]. Diet cost was expressed either per day or per 2000 kcal (i. e. , energy cost). Mean national prices, expressed in euros per 100 g of edible food, were previously obtained from the 2006 Kantar-World Panel database, which gives the annual food expenditures of a representative sample of 12,000 French households  [40].
Statistical Analysis All analyses accounted for the complex INCA2 sampling frame design  [24]. Data were weighted for unequal sampling probabilities and for differential non-responses by region, agglomeration size, age, sex, occupation of the household head, size of the household and season  [13, 24]. All analyses were conducted separately by sex due to the sex-specific EFSA AI of TWI (>2. 5 L for men and >2 L for women). Small, medium, and large consumers were identified based on the tertiles of drinking water intake (including non-consumers). Socio-demographic characteristics were described and statistically compared between tertiles of drinking water intake using the chi-squared test (for qualitative variables) and general linear models (GLM, for continuous variables). Water intakes from fluids and food moisture, expressed in g/day and in percentage of TWI, were evaluated and represented graphically.
A p-value of 5% was used as the threshold of significance. Values are survey-weighted means and adjusted for total energy intake. When specified, adjustments were made for the level of education, socio-occupational status, season, level of physical activity, smoking status, region of residence, and quintile of ICU. Based upon the weighting factors, all results are representative of the French population. Analyses were conducted using SAS version 9. 4 (SAS Institute, Cary, NC, USA).
Several strengths and limitations of this study should be acknowledged. The INCA2 data were collected in 2006-2007 and the observations may already be obsolete. However, INCA2 is still the most recent version of a population-based survey available in France and remains the standard source of reliable information about dietary intakes. Furthermore, between the first version of the national survey (INCA1) and the second (INCA2), the food group 'waters' increased from six items to 50 items, increasing the robustness of data from this food group, which is of particular importance for the present study  [51]. A potential additional limitation could come from numerous low drinking water consumers interviewed during the winter. However, no interaction effect was found between the season and drinking consumption patterns on the level of adequacy (data not shown).
Supplementary Materials: The following are available online at http://www. mdpi. com/2072-6643/8/11/689/s1, Table  S1 : Nine food groups and 27 food subgroups, Table  S2 : Vitamin and mineral intakes by sex and tertile. Acknowledgments: R. G. , J. S. and M. M. have received research grants from Danone Research. R. G. was financially supported by MS-Nutrition and ANRT (Agence Nationale de la Recherche et de la Technology). Author Contributions: R. G. , J. S. , M. M. , I. G. and A. L. were involved in developing the analysis plan, data interpretation and manuscript redaction. Data analysis was performed by R. G. , J. S. and M. M.
Statistical analysis All data are presented as mean ± SEM and were evaluated for statistical significance using Statview version 5. 0 software (Abacus Concepts Inc, Berkeley, USA). Normal distribution was verified using Kolmogorov-Smirnov test. Data for BP, GFR and proteinuria were analysed using 2 way ANOVA testing groups, postnatal age and groups × postnatal age interaction with Bonferoni post hoc analysis when appropriate. Body weight, renal structure parameters were compared between groups using one-way ANOVA with Student-Newman-Keuls comparison test for post hoc analysis. Male and female offspring were analysed separately. The interaction between group and sex was firstly evaluated and showed a sex effect for body weight, BP, parameter of renal functions and structure. A p value <0. 05 was considered statistically significant.
Recent evidence from school children in one province (Kampong Speu) in Cambodia suggests a significant decrease in UIC among schoolchildren  [9]. According to a survey implemented by the French Institute IRD in 2014, the UIC median was 167 µg/L, while in 2011, a survey led by UNICEF reported a median UIC of more than 230 µg/L within the same province and population group  [10]. In Cambodia, data on iodine concentration in urine are sparse or carried out on limited samples of populations. However, the 2014 Cambodian Demographic Health Survey (2014 CDHS) and the Cambodian National Micronutrient Survey 2014 (CNMS-2014) considered this issue, and in doing so, presented the opportunity to obtain national representative data on UIC levels in mothers and children. The present study was carried-out on a subset of mothers and children from the 2014 CDHS to provide information on UIC at the national level in relation to their living area (urban/rural), access to branded iodized salt, ownership of an equity card, and socio-economic status.
Study Design and Sampling The 2014 CDHS is a nationally representative sample of children, aged 0-5 years, and women and men between 15 and 49 years of age. A representative sample of 16,356 households was selected for the 2014 CDHS. The sample was selected in two stages. In the first stage, 611 villages (also known as clusters or enumeration areas) were selected with probability proportional to village size. Village size is defined as the number of households residing in the village. Then, a complete mapping and listing of all households existing in the selected villages was conducted. The resulting lists of households served as the sampling frame for the second stage of sample selection, with households randomly selected for participation in the survey. To provide data on the current micronutrient status of the Cambodian population, a national micronutrient survey (CNMS-2014) was conducted in parallel with the 2014 CDHS.
The CNMS-2014 revisited 1/6 of the main survey clusters of the 2014 CDHS and collected additional data on the micronutrient status of women and children under 5 years of age. In the selected households, urine samples were collected from women who had given birth in the five years preceding the survey and from their children aged 6-59 months. The sample size for this study was estimated to obtain a precision of 3% at the national level and 5% at urban and rural level. The study aimed to recruit a sample of 935 mothers and 1096 children, accounting for 20% non-compliance. The women, who were between 15 and 49 years of age, were selected according to the following criteria: (i) mother of a child aged 6-59 months; (ii) from households having previously participated in the 2014 CDHS; (iii) no evidence of severe or chronic illness, and; (iv) having consented to participate in the micronutrient survey.
The criteria to participate in the survey for children less than five years of age were as follows: (i) from households having previously participated in the 2014 CDHS; (ii) between 6 and 59 months of age; (iii) no evidence of severe or chronic illness (such as high fever, on intra-venous drops, taking tuberculosis treatment), including congenital abnormalities, mental or severe physical handicap, and; (iv) written informed consent signed by at least one parent. Socio-economic status was calculated using the Demographic Health Statistic (DHS) Wealth Index  [11]  to divide households surveyed into the standard three socio-economic groups: the "poorest" (category 1), the "middle" (category 2), and the "richer" (category 3). The Wealth Index was constructed from recorded data on household assets such as tables, chairs, refrigerators, air conditioners, and beds, and also from housing conditions (the materials used for the house's floor, roof, and main walls) and facilities (energy for cooking, electricity and latrines), whilst income and expenditures were not used.
Urine Sampling and Analysis Data were collected at each house in each cluster in the morning. After checking for household and individual codes to match those of the 2014 CDHS, a short questionnaire was taken by the mother/caretaker. Mothers and one of their children (under 5 years of age) were provided with 1 container each for the collection of urine. After obtaining the urine samples, they were stored in cool packs (blue ice), and transported in the afternoon to the provincial health center where they were kept frozen at ´18 ˝C. They were then transported on ice packs within 4 days to the Department of Fisheries Post-harvest Technologies and Quality control (DFPTQ), Ministry of Agriculture, Forestry and Fisheries, Phnom Penh. The samples were thereafter frozen at ´20 ˝C. The urine samples were transported on dry ice to the Institute of Nutrition at Mahidol University, where they were stored at ´20 ˝C while waiting to be analyzed.
Statistical Analysis Data analysis was performed using SPSS software (SPSS, V20; IBM, Chicago, Illinois, USA). In addition to quantitative analysis of the results, values were also categorized into: (I) deficiency as indicated by low UIC (UIC < 100 µg/L); (II) normal UIC (UIC = 100-299. 9 µg/L); and (III) excessive UIC (UIC ě 300 µg/L)  [14]. UIC was not normally distributed (Kolmogorov-Smirnov test) and therefore only non-parametric tests were performed. Median and interquartile range values of the iodine concentrations are presented and disaggregated by wealth index, area of living, access to branded iodized salt, access to iodized salt (according to rapid test kits used during the 2014 CDHS), access to equity card (Households identified as poor in Cambodia receive an "Equity Cards". Poor households can use the equity cards to access a range of services provided by the Government and other organizations.