dataesr/scientific-paragraphs-categorization huggingface dataset:
Timing of maternal deaths An important issue for planning of interventions is an understanding of the timing of maternal deaths with respect to labour and delivery. 47 We completed a systematic review to identify studies of the timing of maternal deaths (appendix). We identified 142 studies and used vital registration, sample registration, and surveillance data for late maternal death. Many studies combined the first 24 h postpartum (immediate or early postpartum) with the intrapartum period, because events of the immediate postpartum period are clinically related to events occurring during labour and delivery. Therefore, we also combined intrapartum and immediate postpartum periods. We followed this format to construct a dataset that included four different time windows: deaths occurring antepartum (before onset of labour), deaths occurring intrapartum or during the immediate postpartum period (up to 24 h after delivery), deaths occurring during the subacute and delayed postpartum periods (24 h to 42 days after delivery),  47  and late maternal deaths (43 days to 1 year after delivery).
Panel: Research in context Our analysis continues a body of analytical work into levels and trends in maternal mortality that began with Hogan and colleagues' report  4  and was followed by that by Lozano and colleagues  5  and the Global Burden of Disease Study 2010 (GBD 2010). 16 ith each subsequent study, there have been important advances in the data available for analysis and the methods of analysis. Lozano and colleagues 5 moved from one preferred regression model, as used by Hogan and colleagues and the UN measurement efforts,  6, 20  to an ensemble of multiple models developed through rigorous out-of-sample predictive validity testing. The maternal mortality analysis included in GBD 2010 extended the analysis in two important ways: maternal mortality was assessed with all other causes of death subject to the constraint that sum of individual causes of death equalled the demographic assessment of all-cause mortality in each age group of reproductive-age women, and it included estimates of the major causes of maternal mortality.
In our study, in addition to 2421 site-years of new data, several important methodological innovations improve the estimation of maternal mortality. First, we have analysed sibling history data for the fraction of reproductive-age deaths that are related to pregnancy by calendar year for each 5-year age group of mothers, pooling data from several surveys when events for the same calendar year were recorded. Second, we have substantially revised the approach to understand the effect of HIV on maternal mortality. We did a systematic review and used relative risks from cohort studies to accurately assign a fairly small fraction of HIV-related deaths during pregnancy or the puerperium to be maternal deaths. Third, we have quantified other direct maternal causes, indirect maternal causes, and late maternal death for the first time.
ACKNOWLEDGMENTS We sincerely thank  Valérie Saint-Giorgio ,  Nicolas Malaty ,  Florent Costilhes ,  Jérôme Antoine  and all the  Centre de Zootechnie  from the  University of Burgundy  for their cooperation. The work was supported by  French   ANR-2010-JCJC-1410-1   MEMOLAP  to  Gérard Coureaud ,  Thierry Thomas-Danguin ,  Frédérique Datiche  and  Guillaume Ferreira.
2-3 weeks prior to experimental procedure, the rats were gradually habituated to a 20 h/day food restriction (FR) schedule in which they had access to food during dark phase only, from ZT16 to ZT20. Since daily fluctuations in glycemia and insulin levels are cued by food intake  (Kaul and Berdanier, 1975; Sitren and Stevenson, 1978) , a single daily meal was imposed to synchronize the circadian variations of glycemia and insulin secretion among the animal cohort. Animals were handled (5 min/day) and weighed daily to assess their adaptation to FR. The daily amount of food consumed was measured for lean and obese rats in order to avoid weight loss and allow stabilization or a small gain of body weight. The daily food distribution schedule was performed by an automatic food distribution system (homemade) piloted by a computer using Matlab software.
When rats perceived ISO in the drinking solution (and consequently avoided it), they licked more pure water during the experimental session, resulting in a higher olfactory detection index. In addition, the number of licks during the first ISO consumption (first licking burst) in the experimental device was recorded. This data allowed us to accurately measure the delay necessary for the animals to be able to detect the aversive ISO diluted in the drinking solution. Data from rats starting the experimental session by drinking at the pure water tube (maximum 2 rats out of 12 per ISO dilution) was excluded from this analysis. In order to exclude a potential bias induced by the number of conditioning sessions on the strength of the COA, a Pearson correlation test was performed between the number of LiCl injections and the olfactory detection index for each animal, for each nutritional status and for each ISO concentration tested.
No correlation was observed (P > 0. 05) for both fa/fa and fa/+ rats. The number of lick during the first burst, the end of the licking burst and the total number of licks at each tube during the experimental sessions were assessed and analyzed using SciPy and MySql database software (Open Source Licenses). A licking burst was defined by a train of high frequency licks (7-10 Hz) and the end of licking burst was determined when the last lick was followed by a period of inactivity lasting at least 1 s.
The sections were washed with 0. 1 M PBS/3% BSA and incubated for 1 h at room temperature with anti-rabbit IgG, anti-mouse IgG, or anti-goat secondary antisera coupled to Alexa 488 (1:100), Cy3 (1:200; Jackson Immunoresearch), or Cy5 (1/100; Jackson Immunoresearch) respectively. After the final wash with PBS, slides were mounted with Vectashield mounting medium containing DAPI for nuclear staining (Vector Laboratories). Images were acquired using a Zeiss Apotome epifluorescence microscope equipped with a digital camera and Axiovision software.
Preparation of electrochemical sensors The glucose biosensor uses glucose oxidase and amperometric detection of hydrogen peroxide  (Vasylieva et al. , 2011). The tip of the probe was coated with glucose oxidase only on 100-150 µm in length  (Vasylieva et al. , 2011)  to target mainly the GL, which thickness is ranging from 100 to 300 µm. Glucose oxidase metabolizes glucose in the extracellular fluid. An oxidation current is thus generated and measured using Neurolabscope software. Each biosensor was connected to a potentiostat, which sent readings of the current generated by glucose in extracellular fluid to a computer. Glucose biosensors have been shown previously to have a range of 0-10 mM with in vitro sensitivity of 1. 6 ± 0. 4 nA/mM (mean ± SEM). To confirm the accuracy of the biosensors, prior to implantation and immediately following testing, biosensor probe were placed in 0.
STATISTICAL ANALYSIS Data are shown as mean values ± SEM. For olfactory detection all percentage measures were transformed using the arcsine square root transformation to normalize the data and stabilize variance  (Sokal and Rohlf, 1981). For behavioral data, Western Blot data, and extracellular glucose measurements, statistical analysis were performed by either a Student's t-test or one-or two-way repeated-measures ANOVA depending on the data set. A Student-Newman-Keuls (SNK) post hoc test was used to complete the analysis when appropriate (Statview software). Physiological parameters (glycemia, plasma and OB insulin level) were analyzed using a non-parametric Mann-Whitney test, or Wilcoxon test when data were paired (Statview Software).
ACKNOWLEDGMENTS This work was supported by  Agence Nationale de la Recherche  Grant  ANR-05-PNRA 1E07  Aromalim, by the  Ministère de la recherche et des nouvelles technologies , by the  Centre National de la Recherche (CNRS)  and the  Claude Bernard University of Lyon (University Lyon1 ). We would like to thank the staff of the  Neurochem facility (Université Claude-Bernard-Lyon I, 69373 Lyon Cedex 08, France) ,  Anne Meiller  for the engineering of the glucose biosensors.
Real-time quantitative PCR analysis According to the manufacturer? s recommendations, total RNA extraction from cells was performed with Nucleospin RNAII kit (Macherey-Nagel) and 1 μg purified RNA was denatured and processed for reverse transcription using Superscript II reverse transcriptase (Life Technologies). PCR amplifications were performed using the Absolute Blue SYBR green fluorescein kit (Roche, Basel, Schweiz) run on a Rotor-Gene (Qiagen, Venlo, The Netherlands). The following primers were used: S6 number: [GenBank:NM_001010]. Forward primer: 5? -CCAAGCTTATTCAGCGTCTTGTTACTCC-3?. Reverse primer: 5? -CCCTCGAGTCCTTCATTCTCTTGGC-3?. TNF-α number: [GenBank:NM_012675. 3]. Forward primer: 5? -CTCATTCCTGCTCGTGGCGGG-3?. Reverse primer: 5? -TACGACGTGGGCTACGGGCTT-3?. TLR2 number: [GenBank:NM_198769.
ELISA The concentrations of TNF-α and IL-6 were determined in rENSpc and human LMMP specimen culture supernatants by ELISA (BD OptEIA? ELISA Set, BD Biosciences, Franklin Lakes, New Jersey, United States) according to the manufacturer's instructions. Absorbance measurements were performed at 450 nm on a spectrophotometric enzyme-linked immunosorbent sandwich assay (ELISA) plate reader (Varioskan? , Thermo Scientific, Waltham, Massachusetts, United States) using the SkanIt software (Thermo Scientific). For human LMMP specimens, the TNF-α concentration was expressed related to the weight of the specimen.
Statistical analysis Data resulted from independent experiments performed in duplicate or triplicate. Statistical significance was evaluated using GraphPad Prism software (GraphPad Software Inc. , La Jolla, California, United States). For time-and dose-dependent experiments, a two-way ANOVA test followed by a Bonferroni post-hoc test was used. The time-dependent response to LPS in Western blots was analyzed with a Kruskal-Wallis nonparametric ANOVA test, followed by Dunn? s post-hoc test. The differences between groups were calculated by a two-tailed Student? s t-test for nonparametric and unpaired data, or by Mann-Whitney U test.
Acknowledgements This work was supported by grants from the  INSERM  ( Institut National  de la Sant? et de la Recherche M? dicale),  Nantes University , the  Centre Hospitalier Universitaire (CHU) of Nantes and la R? gion des Pays de la Loire (NEUROMIC). SC is a recipient of a doctoral fellowship from  Inserm-Pays de La Loire. MRD is supported by the  Centre National pour la Recherche Scientifique (CNRS). MN is supported by a  Contrat d? interface Hospitalier du CHU of Nantes. FC and ED are supported by the  Fondation pour la Recherche M? dicale (FRM).
Therefore, it's likely that the treatment contributed to these events. We agree that international treatment guidelines  [7] [8]  recommend starting triple therapy in HCV genotype 1 patients with compensated cirrhosis. However, these guidelines were based on efficacy and safety data reported in cirrhotic patients included in phase III clinical trials. A crucial point is that low platelets count and hypoalbuminemia were exclusion criteria for these studies, meaning that no safety data was available in such patients at the time of international guidelines. Moreover, it is important to note that patients included in the international telaprevir early access program patients had severe fibrosis (n = 741, Metavir F3 or Ishak 3-4) or compensated cirrhosis (n = 840, Child-Pugh Grade A) and no history of decompensated liver disease.
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter ( pfcrt) and P. falciparum multidrug resistance 1 ( pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemetherlumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ.
METHODS Selection and inclusion of data. Prospective clinical efficacy studies of P. falciparum treatment with AL (six-dose regimen) or ASAQ (three-day fixed dose or loose/co-blistered regimen) with a minimum of 28 days of follow-up and genotyping of pfcrt and/or pfmdr1 were sought for the analysis. Studies were identified by a systematic PubMed literature review using the search terms (artesunate AND amodiaquine) OR (artemether AND lumefantrine) OR (ACT) AND ( pfmdr1 OR pfcrt). Abstracts and text were screened to determine whether inclusion criteria were met. Nine unpublished datasets were also solicited and included in the analysis (see Supplemental Table  3 ). Individual anonymized patient data including baseline characteristics, drug intake, parasite density and temperature were collected.
All but one study included parasite genotyping to identify recrudescent infections of P. falciparum, and all studies assessed the presence of pfcrt and/or pfmdr1 polymorphisms (single nucleotide polymorphisms (SNPs) and copy number variation) in parasites isolated from patients on day 0. Multiplicity of infection and molecular resistance marker data from other days including the day of microscopic recurrent parasitemia were included but were not a prerequisite for study inclusion. Metadata on study location, study design, drugs, and dosing regimens were also gathered. A schematic of the patient numbers and overall flow of the study is shown in Figure  1. Data curation and generation of variables. All data sets were uploaded to the WorldWide Antimalarial Resistance Network repository and standardized by using the WorldWide Antimalarial Resistance Network Data Management and Statistical Analysis Plans (DMSAP).
RESULTS Individual patient and linked parasite genotype data from 31 studies were available (Supplemental Table  3 ). Data from 7,249 patients who were treated with AL (5,003) or ASAQ (2,246) were included in the analysis. Twenty seven studies were published, representing 91% of all published clinical data on AL and ASAQ in which pfcrt or pfmdr1 genotypes were determined. Baseline characteristics for patients treated with AL or ASAQ are shown in Supplemental Table  4. Clinical efficacy of AL and ASAQ. The estimates of efficacy (defined as risk of PCR-adjusted recrudescence) of AL and ASAQ are shown in Table  2. Of the 5,003 AL patients, 4,763 were followed-up for at least one day and were included in the analysis. Similarly, of the 2,246 ASAQ patients, 2,099 were included. In total, 1,107 patients had recurrent parasitemia after treatment with AL, of which 188 (18%) were classified by PCR as having recrudescent infections.
2014. Accepted for publication April 22, 2014. Published online July 21, 2014. Note: Supplemental tables appear at www. ajtmh. org. Financial support: The WorldWide Antimalarial Resistance Network is supported by the Bill and Melinda Gates Foundation. Disclaimer: The opinions and assertions contained herein are the personal opinions of authors and are not to be construed as reflecting the views of the U. S. Army Medical Research Unit-Kenya or the U. S. Department of Defense.
Received January 14 , 14 2014. Accepted for publication April 22, 2014. Published online July 21, 2014. Note: Supplemental tables appear at www. ajtmh. org. Financial support: The WorldWide Antimalarial Resistance Network is supported by the Bill and Melinda Gates Foundation. Disclaimer: The opinions and assertions contained herein are the personal opinions of authors and are not to be construed as reflecting the views of the U. S. Army Medical Research Unit-Kenya or the U. S. Department of Defense.
Acknowledgements This research was founded by the  Third World Academy of Science (TWAS Fellowship  for Research and Advanced Training FR number: Grant No. 3240224121  and the  International Foundation for Science (IFS, Stockholm, Sweden)  and the  Organization for the Prohibition of Chemical Weapons (OPCW)  ( IFS Research Grant   N0 F/4921-2 ) offered to  Dr. Ngbolua K. N.
1 ). [23] e then extended our separation protocol by SFC to some other fluoroalkylated compounds (Table  1 ). Each enantiomer of dichlorofluoromethyl-and bromodifluoromethyl sulfoximines 7 and 8 was separated (entries 3 to 6) and independently transformed into their corresponding sulfur (vi) derivatives. The enantiomeric purity of each sulfoximine 9a,b and 10a,b was ensured by analytical SCF or HPLC. Table  1  summarizes the optical rotation of the 12 enantiomers obtained in our study. The absolute configuration of the monofluoroand difluoromethyl sulfur derivatives was attributed by analogy with the data (retention time and X-ray analysis) collected for the trifluoromethyl series. The first isolation of the trifluoromethyl phenyl sulfoximine 6b strongly encouraged us to prepare an enantiomerically pure version of Shibata's reagent 12 (Scheme 4).
1% formic acid in methanol. The entire experiment was controlled by Aria operating software 1. 1. 1. In the first step, 30 μL supernatant from the sample preparation was injected and loaded onto a C18 XL TurboFlow column (50 mm × 0. 5 mm internal diameter (i. d. ), ThermoFischer Scientific) under turbulent flow (100% B, 1. 5 mL/min, 30 s). In the second step, retained analytes were flushed from the TurboFlow column using an elution solvent (A-C, 97/3, v/v) stored in a holding loop and focused through a Tee piece on to a Hypersil Gold C18 analytical column (3-μm particle size, 100 mm × 2. 1 mm i. d. ; ThermoFischer Scientific). In the third and fourth steps, during gradient elution (A-C, 97/3 to 10/90 v/v) from the analytical column, the TurboFlow column was washed with eluent C (100%). In the fifth step, the loop was refilled with the elution solvent (A-C, 97/3 v/v) while the chromatographic separation was proceeding on the analytical column.
Discussion We performed an analytic study assessing the residual methadone dosage left in empty bottles by treated patients. It shows that the mean residual quantity of methadone left in each bottle is 1. 9 ± 1. 8 mg, but 3. 2 ± 2. 3 mg in the sample of 60-mg bottles. Therefore, in a context of increase of methadone prescription in France and of an already observed increase of accidental and non-accidental ingestion of methadone in childhood in other countries  [15] , the potential risk of accidental overdose in case of ingestion of such bottles by a child cannot be ruled out. Although, no intoxication with empty methadone bottles was ever reported in French pharmacovigilance databases, we suggest that this hazard needs to be taken into account, and there are several easy ways to implement harm reduction policies.
Cyclosporin is an effective immunosuppressant used in renal transplantation  [38]. Clinical trials have found oxalaplatin to be effective as a component of combination therapy for advanced colorectal cancer  [39, 40]. The antiretroviral drugs azidothymidine and zidovudine were shown to improve survival with AIDS in randomized clinical trials  [41]  For these specific innovations, a questionnaire was developed and answered by the participating partners from the United Kingdom, the Netherlands, Germany (West Germany), France, Spain, Estonia and Sweden. The partners collected data from official sources and from key informants. Information was sought on the first introduction of the innovation and the period of implementation. For the first part, documents on the official and organized introduction were asked for.
These were for instance, the registration year for pharmaceuticals as well as the year of national programs and guidelines. To get information on the implementation of the interventions, data on scientific or committee reports evaluating the implementation were requested. For pharmaceuticals, sales statistics were collected, if available. This data was used to verify that the medicine has been available in the respective country and also to indicate the speed of the implementation. To facilitate comparisons between countries, statistics on daily defined doses (DDD)  [42]  were asked for. Sales statistics were available from Sweden (1977-2008; only from year of registration),  Estonia (1999 Estonia ( -2008)) , Germany (1999-2008; hospital prescribing and privately insured patients were unavailable)) France  (2002) (2003) (2004) (2005) (2006) (2007) , United Kingdom (mainly 1999; hospital prescribing unavailable) and Spain (2000-2008; hospital prescribing unavailable).
The measure used differed between countries and pharmaceuticals. Sales statistics measured by DDD was available for most of the period from Sweden, Estonia and Germany only. In addition, a literature review was performed for each innovation and country. Articles registered in Medline with any of the key words (or words in title or abstract) 'standards, guidelines, official policy, consensus development, evaluation studies or clinical trial' in combination with the terms for the innovation and the country names were scrutinized for applicable information. The country representatives were asked to comment on the data found and to collect further data based on the information. The data from the questionnaire and literature review were combined in order to get several indicators of the diffusion process of the specific innovations in each country.
Criteria 2: In order to define the start of the diffusion, we also judged that data indicating a continued diffusion of the drug was needed. This was indicated by further clinical trials, evaluation reports, guidelines and sales statistics. Thus, several data was used for each statement of the year of introduction. We present in this article the references to the early indicators of the start of diffusion and to evaluation reports and guidelines indicating the further diffusion of the pharmaceuticals. The availability of sales statistics was presented above. When data was available, we analysed the year when the peak level of sales of the pharmaceutical occurred and the diffusion time from start of diffusion to this year. Further references are available in the Amiehs report  [27]  on the Internet.
Results Iridoid gene discovery. We previously reported the assembly of CathaCyc, a C. roseus metabolic pathway database based on Illumina HiSeq2000 RNA sequencing data  16. The data set was derived from C. roseus suspension cells and shoots treated with the plant hormone methyl jasmonate  16. Here we complemented this data set with RNA-Seq data from cell suspensions overexpressing either ORCA2 or ORCA3, transcription factors that regulate the expression of LAMT, SLS and several other genes in the MIA biosynthesis pathway  17  , but not GES and G8O (Fig. 2a ). These four and all other known MIA genes are induced by MeJA both in cell suspension cultures and whole C. roseus plants, although GES/G8O and LAMT/SLS show different induction characteristics (Fig. 2b ). Furthermore, GES, G8O and IS are expressed in the internal phloem-associated parenchyma (IPAP) cells, whereas LAMT and SLS are expressed in the leaf epidermis  [10] [11] [12] [13] 18, 19.