dataesr/scientific-paragraphs-categorization huggingface dataset:
We previously reported the primary and secondary outcomes of a placebo-controlled phase II trial (NCT00890825) of second-line selumetinib (AZD6244, ARRY-142886), an orally available, potent, selective, non-ATP-competitive MEK1/2 inhibitor, þ docetaxel treatment in patients with KRAS mutant NSCLC (Ja ¨nne et al, 2013). Median overall survival (OS; primary endpoint) in the selumetinib group was 9. 4 months and 5. 2 months in the placebo group (hazard ratio (HR) 0. 80, 80% confidence interval (CI): 0. 56-1. 14). Treatment with selumetinib þ docetaxel significantly improved PFS, objective response rate (ORR) and patient-reported outcomes compared with docetaxel alone, but was associated with increased adverse events relative to docetaxel þ placebo. Here, we report the results of a retrospective analysis of the impact of different KRAS codon mutations or combinations of codon mutations on efficacy outcomes in this phase II trial.
MATERIALS AND METHODS Methodology of this trial (clinicaltrials. gov NCT00890825) has been previously described  (Ja ¨nne et al, 2013). In brief, this doubleblind, placebo-controlled, randomised, global phase II study included patients with histologically or cytologically confirmed, locally advanced or metastatic, KRAS mutant NSCLC (stage IIIB/ IV), following failure of first-line chemotherapy. Treatment consisted of intravenous docetaxel 75 mg m À 2 on day 1 of every 21-day cycle in combination with either selumetinib hydrogen sulphate capsules 75 mg orally twice daily or matched placebo until disease progression or unacceptable toxic effects occurred. KRAS mutation status was confirmed before randomisation by an AstraZeneca-appointed central laboratory with TheraScreen K-RAS ARMS Mutation Kit (Qiagen (formerly DxS Ltd), Manchester, UK), or by an AstraZeneca-agreed local laboratory with agreed methods, or an accredited commercial laboratory with proprietary-accredited methods.
A retrospective statistical analysis was undertaken on data to investigate MG associations within the endpoints of OS, PFS, change in tumour size at week 6 and ORR. OS and PFS were analysed by Cox proportional hazard modelling, while tumour size was analysed by an additive linear model. Both analyses incorporated model terms to account for World Health Organization performance status, sex, histology and smoking status. Analysis of MG effect upon response was undertaken using a model that incorporated a term for treatment:MG interactions. Significant MG associations were defined as nominal P-values of Po0. 05 for the treatment:MG interaction term within the model. Analysis of specific codon effect upon response was undertaken using a model that incorporated a term for treatment:codon interactions.
G12C or G12V mutations have greater sensitivity to selumetinib warrants further investigation in future clinical trials. A randomised, double-blind, placebo-controlled phase III trial (SELumetinib Evaluation as Combination Therapy-1 (SELECT-1) study; NCT01933932) of selumetinib þ docetaxel in second-line KRAS mutant advanced NSCLC is now recruiting patients, and will provide an opportunity to further evaluate the impact of specific KRAS mutations.
G12C or G12V mutations have greater sensitivity to selumetinib warrants further investigation in future clinical trials. A randomised, double-blind, placebo-controlled phase III trial (SELumetinib Evaluation as Combination Therapy-1 (SELECT-1) study; NCT01933932) of selumetinib þ docetaxel in second-line KRAS mutant advanced NSCLC is now recruiting patients, and will provide an opportunity to further evaluate the impact of specific KRAS mutations. A 1. 0 G12V (n = 6/9) G12D (n = 11/18) G12C (n = 27/38) MG2 (all mutations other than G12C and G12V) (n = 23/36) Overall survival (probability) MG1 (G12C and G12V) (n = 33/47) 0. 2 0. 4 0. 6 0. 8 HR 1. 32 (0. 37-4. 68) HR 2. 26 (0. 95-5. 34) HR 0. 59 (0. 35-1. 00) HR 0. 96 (0. 54-1. 70) HR 0. 69 (0. 44-1. 09) MG1, selumetinib + docetaxel MG1, placebo + docetaxel MG2, selumetinib + docetaxel MG2, placebo + docetaxel n 24 23 19 17 Events Median (days) 17 16 12 11 292 133 262 215 Median (months) 9.
Data extraction, quality assessment and analysis The two reviewers (MS and AC) independently read the entire texts of the retrieved reports and rated study quality using well-established criteria  [21, 22]. RCT quality was graded using a nine-point scale combining elements from Jadad's  [21]  and Chalmers'  [23, 24]  scales, whereas the quality of case-controlled studies was appraised using the Newcastle-Ottawa scale  [25]. In addition, both reviewers extracted the following data: First author, year of publication, country, study design, number of patients, demographic data, pre-ECMO ventilation and blood gas data and outcomes. Because of very high heterogeneity between studies, related to different generation ECMO and ECCO 2 R devices used in the last 40 years, different patient populations evaluated, and the scarcity of randomized or quasi-randomized trials (most of which were flawed by major methodological limitations) performed with the latest generation extracorporeal gas exchange techniques, we did not perform meta-analyses of randomized or quasi-randomized trials and choose to report and discuss only crude study results.
Volume-outcome effect and ECMO activity organization Recent analyses of large pediatric databases have suggested a significant relationship between the volume of patients treated by center and ECMO patient prognosis  [53] [54] [55]. ECMO case-series published after the pandemic influenza A(H1N1) might also allow a comparative analysis of worldwide results obtained for a very homogeneous disease (Tables  4  and 5 ). These data suggest that the best results were obtained for patients managed in expert centers treating a sufficient number of patients and in countries where ECMO activity was organized and regulated, as was the case in the United Kingdom  [56] , Italy  [57]  and in Australia and New Zealand  [58]. A recent position paper  [59]  by an international group of physicians with expertise in ECMO for severe respiratory failure advocated for regional and interregional organization of ECMO activity through networks of hospitals around an ECMO referral center with a mobile ECMO unit  [34, 60, 61]  to retrieve the most severe ARDS patients.
Although early implementation of VV-ECMO in severe ARDS patients might allow significant reduction in ventilatorinduced lung injury (VILI) and may rescue patients dying of refractory hypoxemia, more evidence is urgently needed to evaluate the actual impact of the technique on patientcentered outcomes compared to optimization of conventional treatments, including prone positioning  [2]. This is the main objective of the ongoing international multicenter randomized Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial (ClinicalTrials. gov Identifier: NCT01470703), which will test the efficacy of early VV-ECMO in patients with severe ARDS with tight control of mechanical ventilation in the control group, initiation of ECMO prior to transportation to ECMO centers, and the use of ECMO in every patient randomly assigned to receive it  [71].
Acknowledgement Matthieu Schmidt was supported by the  French Intensive Care Society (SRLF) , the  "Fonds de dotation Recherche en Santé Respiratoire , 2012", the  "Collège des Enseignants de Réanimation Médicale"  and the " Département du Développement professionnel continu médical -Assistance publique-Hôpitaux de Paris ".
Acknowledgements Financial support by the  European Research Council  ( ERC-320441-Chirallcarbon ),  Ministerio de Economía y Competitividad (MINECO) of Spain  (projects  CTQ2011-24652  and  CTQ2012-31914 ), the  Comunidad Autónoma de Madrid  ( FOTOCARBON  project  S2013/MIT-2841 ), the  Generalitat Valenciana  ( PROMETEO/2012/053 ),  European FEDER  funds ( CTQ2012-31914 ) and the " Solar Technologies Go Hybrid" initiative by the state of Bavaria  is acknowledged. L. M. thanks the  Obra Social "la Caixa " for a postgraduate fellowship. J. C. acknowledges the  Ministerio de Educación, Cultura y Deporte (MECD) of Spain  for an  FPU grant. N. M. thanks the  Alexander von Humboldt Foundation.
Methods The central assumption made was that SA could have feasibly screened about 58 000 women with VIA in five years like Zambia did. Since SA has a Pap smear screening coverage of approximately 13. 6% in 3 years for women aged 18-69 years,  [2]  it was assumed that of the 58 000 women that SA could have screened with VIA only 44 853 not screened by Pap smear could have benefited from VIA. And about 85%  [7]  of these 44 853 women could have been treated successfully (Figure  3 ). Data for the expected proportion of high-grade cervical cancer precursor lesions in VIA screened and a control (unscreened) population was obtained from a South African study reported in 2005. [4] ta on the expected incidence and mortality from cervical cancer in a VIA screened (single round of screening) and a control (unscreened) population was obtained from an Indian study reported in 2007.
[10] uth Africa's population is approximately 3. 5 times that of Zambia's (with females being almost half the population in both countries). [15] The final assumption made was that SA could have screened a similar proportion of women as Zambia, thus the estimates were multiplied by 3. 5. These data were used to estimate the number of highgrade cervical cancer precursor lesions, new cases and deaths from cervical cancer that could have been prevented had SA implemented a VIA screen and treat (cryotherapy) or refer strategy. Ethical approval for this study was not required because publicly available data was used for estimation.
The scattered x-rays were detected using a Pilatus 100 K Detector (Dectris) with pixel size of 172 3 172 mm 2 and only a horizontal detector slit of 300 mm in front of it. The scattered intensities were then plotted as function of in-plane and out-of-plane components (q xy , q z ) of the momentum transfer vector (q) which is related to the in-plane angle (Q) and out-of-plane angle (h f ) respectively  [30] [31] [32] [33]. This particular detector-slit configuration facilitated the detection of scattered data as a function of h f , similar to 1D position sensitive detector (PSD) as shown in Fig. 2 (a)  34. The two-dimensional (2D) GIXS patterns were obtained by scanning the detector along Q. The intensity distribution along q xy and q z provides substantial information about the in-plane and out-of-plane structures  [31] [32] [33]  respectively.
This is a clear signature that some preferred orientation of the crystalline planes occurs as a result of some movement of the crystallites over water surface within the coherent scattering volume despite the fact that during the process of data acquisition the barriers were locked after having reached the desired surface pressure. The x-ray data were collected carefully for short duration of time and regular change of sampling area was done to avoid beam-damage  33. AFM measurements (Nanoscope IV, Digital Instruments) were carried out in tapping mode using etched Si cantilever on thin films of TBPOSS (pre and post phase transition) after transferring horizontally on hydrophilized Si substrate.
Summary and Conclusion Characteristic phase transition has been observed for TBPOSS monolayer on water surface. The isotherms in consequent cycles were reversible and in each cycle the phase transition occurred at the same area per molecule and pressure as previous cycles. GIXS measurements have been performed on monolayer of TBPOSS before and after transition. GIXS data show that the TBPOSS monolayer exhibits a rare reversible non-equilibrium crystalline phase on lateral compression. The crystal structure obtained here using GIXS measurements is different from the one obtained by conventional powder diffraction measurements for TBPOSS  29. Although the crystal structure and symmetry were the same as reported, we observed a constricted lattice for the triclinic structure. GIXS measurements are consistent with AFM measurements done on films transferred both before and after the phase transition.
Acknowledgments Authors are grateful to  Prof. J. Matisons ,  School of Chemical and Physical Sciences, Flinders University, Adelaide 5001, Australia  for providing the TBPOSS samples. R. Banerjee ,  M. K. Sanyal  and  M. K. Bera  acknowledge  Department of Science and Technology India  for full financial support to perform experiments at  APS, ANL, USA. A. Gibaud  and  M. K. Sanyal  acknowledge the support of  Indo French Centre for the Promotion of Advanced Research  ( CEFIPRA/IFCPAR ) for exchange visits under project No. 3808-3. ChemMatCARS Sector 15 is supported by the  National Science Foundation  under grant number  NSF/ CHE-1346572. Use of the  Advanced Photon Source , an  Office of Science User Facility  operated for the  U. S. Department of Energy (DOE) Office of Science by Argonne National Laboratory , was supported by the  U.
7±0. 3, ] [26]  The fibers were then harvested and dried, and respiration rates were expressed as µmol O 2 /min/g dry weight. All reagents were purchased from Sigma-Aldrich Co. (St Louis, MO, USA), except ADP, which was obtained from Boehringer Ingelheim (Ingelheim, Germany). Data are reported as the mean ± standard deviation. The apparent Km of mitochondria for O 2 (for the two types of water and with the two electron donors) and for ADP (for the two types of water and glutamate-malate) were calculated using nonlinear regression of the individual relationships between O 2 or ADP concentration and Vmax, using a Lineweaver-Burk plot. The apparent Km for O 2 (Km O 2 ) was compared using a two-way analysis of variance (ANOVA) (water × electron donor), while the apparent Km for ADP for the two waters was compared using one-way ANOVA.
CTC detection has already been shown to be an early marker for disease progression with prognostic relevance after the start of treatment for metastatic disease [55e57]. Further ongoing trials (e. g. SWOG 0500 and NCT01185509) should clarify the role of CTCs in the management of patients with breast cancer and confirm its utility for both monitoring the efficacy of treatment and as a predictive tool. ctDNA, analyzed by multiplex tumor mutation sequencing, has also been shown to be a non-invasive means of monitoring disease progression, with higher concentrations being correlated with worse OS  [58, 59]. Assessment of such circulating blood biomarkers holds great promise for the future, though their routine incorporation into clinical trials will require the development of robust standardized assays.
3 More than one spatially separate population is strongly encouraged but not required, as the ability to estimate among-population (or intraspecific) variation would be beneficial. Single populations can be included, but the overall aim of the network is best met with data from multiple populations of each study species. 4 Walk the perimeter of the invaded area with a GPS to generate an area (GIS polygon). Population boundaries should be estimated based on your study system. For example, a sterile clonal forb may have a smaller isolation distance (i. e. , distance separating two populations) than an outcrossing grass. Include the population size in your dataset, and specify your isolation distance. Reassess the population size every 3 years with attention to average horizontal error. 5 Record the following for each of your populations: a state, province, or territory, and country; b latitude, longitude (decimal degrees), and elevation; c ecosystem (e.
Plot size The plot size should scale with the size of the target invader and should be based both on invader size and logistical constraints. Plots should be at least 1 9 1 m for most grasses and forbs, and we suggest 5 9 5 m, 10 9 10, or 20 9 20 m for shrubs and trees. Ecological impact metric data are collected in each plot, which will be surrounded by a border to reduce edge effects. Removal plots should have a border proportional to the height and root system of the invader and be at least half the extent of the plot size. For example, the border for common reed (Phragmites australis) would likely be much larger than for garlic mustard (Alliaria petiolata) due to size differences and life history-related characters of size and underground organs.
Sampling Key features of the community and ecosystem were selected to represent important pools and fluxes that are commonly associated with terrestrial invasive plants ª 2015 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. (Ehrenfeld 2010; Vil a et al. 2011). The included metrics are relatively simple to measure, cost-efficient, and implicated in ecosystem function. All coordinated distributed experiments require a balance of sample depth and breadth with participant expense and expertise  (Colautti et al. 2014). Therefore, we include both core (Table  1 ) and optional measurements (Table  2 ; see also  Kumschick et al. 2015). Most data will be collected within the interior of each plot to reduce edge effects. While invader removal treatments are implemented throughout the year, measurements are made and samples collected at peak community productivity, which will vary among systems.
2011). Multivariate methods could also be employed to integrate across metrics to compare differences among invaded, uninvaded, and removal across time (e. g. ,  Barney et al. 2013). Data can be analyzed within an individual study, or across studies, with various levels of nesting included as appropriate. With sufficient data from different sites, climatic variables could be included to evaluate whether and how patterns of impacts vary across regions from different bioclimatic zones. For species with adequate spatial replication, we could also explore the relationship between invader cover and response variables (Fig. 3 ), which is predicted to be nonlinear (e. g. , McCarthy 1997), but is rarely explored empirically  (Barney et al. 2013 ). An important advantage of the GIIN protocol is allowing investigation of invader impacts with respect to invader cover (Fig.
Acknowledgments The nucleus of this paper was conceived at the Andina International Workshop 2012 partially funded by  USDA AFRI SAS-LTAP  Proposal number  2009-03114  (BDM) attended by JNB, AP, MN and BDM. JNB would like to acknowledge the  USDA   Controlling Weedy and Invasive Plants program  grant  2013-67013-21306 , and  USDA Hatch. DRT would like to acknowledge the  Virginia Tech CALS   Teaching Scholar program  for support. RAH acknowledges the support of  NSF   RCN grant  no. 0541673 , the  USDA , and the  Colorado Experiment Station. PLS was supported in part by a grant from  Larimer County ,  Colorado. MAN, RDD , and MNBG want to acknowledge the Bio # 5 GEF 090118  grant. AP funded by grants Fondecyt  1140485 , ICM  P05-002 , and  CONICYT PFB-23. AP thanks insightful comments by  Rafael Garc  ıa and Ana C obar-Carranza.
JNB would like to acknowledge the  USDA   Controlling Weedy and Invasive Plants program  grant  2013-67013-21306 , and  USDA Hatch. DRT would like to acknowledge the  Virginia Tech CALS   Teaching Scholar program  for support. RAH acknowledges the support of  NSF   RCN grant  no. 0541673 , the  USDA , and the  Colorado Experiment Station. PLS was supported in part by a grant from  Larimer County ,  Colorado. MAN, RDD , and MNBG want to acknowledge the Bio # 5 GEF 090118  grant. AP funded by grants Fondecyt  1140485 , ICM  P05-002 , and  CONICYT PFB-23. PP and MV were supported by long-term research development project  RVO 67985939  ( Academy of Sciences of the Czech Republic ). PP acknowledges support from project no. P505/11/1112  ( Czech Science Foundation ) and  Praemium Academiae  award from the  Academy of Sciences of the Czech Republic.
We acknowledge the  Helmholtz-Zentrum-Berlin Electron storage ring BESSY II  for provision of synchrotron radiation at the ISISS beamline and we thank the  BESSY  staff for continuous support of our experiments. R. S. W. acknowledges a  Research Fellowship  from  St. John 's College, Cambridge. S. H. acknowledges funding from  ERC  grant  InsituNANO  (No. 279342 ) and  EPSRC  grant  GRAPHTED (EP/K016636/1 ). P. S. acknowledges the  Institut Universitaire de France  for a junior fellowship. This research was partially supported by the  EU   FP7 Work Programme  under Grant GRAFOL (No. 285275 ) and  Graphene Flagship  (No. 604391 ).
Stromme et al. found that children with severe ID were from higher socioeconomic backgrounds than children with less severe forms  [17]. In some cases no relationship was found for the more severe forms of ID  [16]. Other studies suggested that only isolated ID was associated with SES, unlike ID associated with other serious neurological conditions  [15] [16] [17]. Given discrepancies and potential for targeting specific groups, the relationship between SES, autism and ID needs to be clarified. We based our study on the data of a population-based registry in France, which has universal and free social health coverage. Area socioeconomic indicators used as proxies of individual SES of families were considered. The objective was to investigate the links between SES and the prevalence of: 1) ASD with or without ID, whatever the severity of ID; 2) severe ID without ASD.
Case Identification This study included children aged 8 from the childhood disability registry of the administrative area of Haute-Garonne, south-western France. Children born between 1995 and 2004 were selected. The main data source was the local public authority fully responsible for support, guidance, and aid to education for all children living in the surveillance area. Other data sources were child psychiatry departments. Case status was determined by a physician after a comprehensive review of all clinical records available after parental approval as required by national law. For the main administrative data source the informed consent of the parents of all children being registered was sought before consulting the medical record, independently of whether their child was diagnosed with ASD or not.
Discussion We reported significantly higher prevalences of ASD with ID in areas with the highest level of deprivation and the highest percentage of unemployed adults, persons with no diploma, immigrants and single-parent families. For ASD without ID, a higher prevalence was found only in areas with the highest percentage of immigrants. The prevalence of isolated severe ID tended to increase across the tertiles of socioeconomic level (least deprived to most deprived) captured by all the indicators studied. The two groups of children with ID had similar gradients of risk of elevated prevalence at the highest level of deprivation. This study was conducted using a population-based database designed to be comprehensive, even if some of the few families that refused to participate may have had a child with an ASD or a severe ID diagnosis.
Acknowledgments The CARIPLO foundation is acknowledged for financial support through the grant  EIDOS 2011-038. The fabrication of the device was performed at the nano-center  CTU-IEF-Minerve , which is partially funded by the  "Conseil Général de l'Essonne ". This work was partly supported by the  French RENATECH network. D. M-M. acknowledges support by the  Institut Universitaire de France. Marie Curie International Outgoing Fellowships  through grant agreement PIOF-GA-2013-629292 MIDEX is partly acknowledged. This project has received funding from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme  (grant agreement  N°639107-INsPIRE ).