dataesr/scientific-paragraphs-categorization huggingface dataset:
Comparison with the observed activity pattern Here we compare the structures generated with our parameterized model to the observed structures used in Paper II. To do this, we use the spot and bright feature lists over cycle 23 that we retrieved from sunspot catalogues and MDI/SOHO magnetograms, respectively (Paper II). These data sets have some gaps, leading to a coverage of 3586 days, for a total duration of 4171 days, whereas our simulations have a length of 12. 5 yr with a daily sampling, i. e. 4566 days (length of cycle 23). We therefore applied the same calendar as in Paper II to our outputs so as to make a relevant comparison. The full time series will be studied in Sect. 4.
The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsons disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons.
Surgery and intraoperative microrecording Implantation of the deep brain stimulation system was performed separately in two steps: (i) stereotactic insertion of the permanent quadripolar electrode into the STN bilaterally and (ii) implantation of connection leads and the neurostimulator to the subclavial region. The Leksell frame and SurgiPlan software system (Elekta, Stockholm, Sweden) were employed in the stereotactic procedure. Pre-surgical planning was based on 1. 5 T MRI with direct visualization of the target. The central trajectory was intentionally focused on the STN center near the anterior part of the red nucleus (15 patients) or to the posteroventrolateral portion of the GP interna (4 patients). The first surgery was performed while awake under local anesthesia. The extracellular neuronal activity was mapped by conventional microelectrode recordings (MER) using parallel insertion of five tungsten microelectrodes spaced 2 mm apart in a ''Ben-gun'' configuration to select sites for the macroelectrode intraoperative stimulation  [26, 27].
FISH Probes. e 5S ribosomal probe corresponds to a partial sequence (87 bp) of the highly conserved 5S rRNA coding region, obtained from the genomic DNA of Chionodraco hamatus as described by Ghigliotti et al. [23]. A DNA fragment (1218 bp), obtained from the notothenioid Dissostichus mawsoni shotgun library of the BAC plasmid DmBAC64 (  [22] , AFGP gene H2A7 in GenBank accession number HQ440760), and encoding for the repetitive (r-Ala/Pro-Ala)n AFGP polyprotein sequence, was used as the AntiFreeze GlycoProtein (AFGP) probe. T 1: Information on the site of sampling and size of the samples used in the cytogenetic analyses. M: male, F: female. e 5S rDNA and the AFGP probes were nick translation labeled with biotin-16-dUTP (Roche) according to standard procedures, ethanol puri�ed, and dissolved in the hybridization buffer (50% formamide/2X SSC, 40 mM, KH2PO4, 10% dextran sulphate) to a �nal concentration of 15 ng/L and 20 ng/L respectively.
Acknowledgments e study was supported by the  Italian National Programme for Antarctic Research (PNRA)  and contributes to the  SCAR Scienti�c Research Program EBA  ( Evolution and Biodiversity in Antarctica ). Part of  L. Ghigliotti 's work was supported by the  L'Oreal-UNESCO program  " For Women in Science" through the 2008 National Fellowship "L'Oreal Italia Per le Donne e la Scienza. " C-HCC acknowledges  NSF OPP  for grant award that supported parts of this study. e authors gratefully acknowledge  Catherine Ozouf-Costaz  ( Département Systématique et Evolution, MNHN Paris ) for her comments and supervision of the work at the MNHN.
Future studies Despite agreement across the uro-radiology community that mpMRI has a potential future in the standard diagnostic pathway for CaP, differences in current conduct, interpretation, and reporting of mpMRI renders reliable comparison of research studies difficult  [25, 26]. This is currently an impediment to widespread and effective adoption of this technique. However, there are signs of change. Consensus now exists on the minimal and optimal imaging standards for mpMRI  [25] , and clinical practice guidelines have recently been produced  [27]. Once agreed, standardized mpMRI protocols and reporting schemes will require validation within prospective studies that evaluate the ability of mpMRI to detect, localize, and characterize CaP against an appropriate reference standard. Such a trial is due to start imminently (http://clinicaltrials.
gov NCT01292291). Targeting of biopsies to lesions identified on mpMRI is already in clinical use in a number of centers, but the techniques adopted are varied. Some groups use 'cognitive' registration of the results of the mpMRI to target biopsies on TRUS or transperineal prostate biopsies  [28]. Prostate distortion and poor interpretation of imaging are potential limitations. Other groups are evaluating 'in-bore' targeting of lesions within the MR scanner, and have demonstrated improved cancer detection rates  [5, 6] , and risk stratification of disease  [29] , compared with standard TRUS biopsies. However, this technique carries a high burden on imaging resources and time, and usually requires a general anesthetic. An alternative approach is to register MR images onto an ultrasound platform, to allow real-time targeting of lesions in the theater or out-patient clinical setting  [11].
Using DNA barcodes for assessing diversity in the family Hybotidae (Diptera, Empidoidea) efficient (correct) identification. Therefore, extra efforts are needed to increase the representation of hybotids in these databases. Second, the spatial scale of sampling has to be taken into account, and especially for widespread species or species complexes with unclear taxonomy, an integrative approach has to be used to clarify species boundaries and identities. With over 11,400 described species, the superfamily Empidoidea represents one of the largest extant lineages of flies (Diptera, Brachycera)  (Evenhuis et al. 2007 , Pape et al. 2009). According to the most recent systematic revision  (Sinclair and Cumming 2006) , this superfamily comprises five families: the Atelestidae, Brachystomatidae, Dolichopodidae sensu lato, Empididae and Hybotidae.
It has been made possible by extensive field collections carried out by the senior author (P. G. ), who has added substantially to material currently available from the Old World. DNA barcoding  (Hebert et al. 2003) , based on a ca. 650 bp DNA region from the 5' end of the mitochondrial COI gene, is an easy-to-use molecular approach that allows quick assignment of samples into 'genetic' groups. In situations where a reference database of specimen data and morphospecies identifications exists, this technique can be used for exploring and comparing species limits as defined by morphological vs. DNA-based criteria. Although the family Hybotidae is species-rich, genetic data (i. e. , DNA barcode sequences) for this group are surprisingly scarce in public databases, such as GenBank and The Barcode of Life Data Systems -BOLD  (Ratnasingham and Hebert 2007).
While there are over 500 COI sequences of Empidoidea in GenBank, we could only find a single, correctly classified Hybotidae sequence. Furthermore, although there are several DNA barcoding projects underway in North America that are analyzing large numbers of Hybotid species, sequence data from these studies have yet to be made available to the public. We found four DNA barcode sequences of hybotids in BOLD, but these are from specimens collected in Canada, and therefore fall outside the geographical scope of our study, which is restricted to Old World taxa. In the current paper, we optimized protocols for DNA barcoding of hybotid flies and performed a preliminary barcoding study on selected genera and species of this group. We hope that this approach will accelerate an inventory of hybotid flies.
Results Our sampling covered all the currently accepted subfamilies and tribes of the Hybotidae. At the generic level, we investigated 22 of the 66 known genera (see Table  1  for full details). The DNA sequence data set consisted of 341 COI sequences (339 Hybotidae and two Empididae), each sequence being of 657 bp in length. These sequences were deposited in BOLD and GenBank (BOLD Process IDs EMPID001-13 -EMPID341-13). An NJ tree without species names and additional sample information is shown in Figure  1  (a fully annotated tree is shown in Supplementary File 2). 'Species-level' groups (i. e. , close to or at terminal nodes) were generally well supported, while deeplevel groups were not (see Figure  1  and Supplementary File 2). Especially when low intraspecific distance was observed, these groups (considered as molecular operational taxonomic units -MOTUs) often received 100% bootstrap support.
2006 , best match and best close match criteria). An inherent problem with dipterans is the possibly high amount of unknown diversity on a global scale leading to incomplete databases, the substantial age of some large radiations that is linked to (very) high mitochondrial sequence diversity, and the limited taxonomic expertize on particular groups hampering successful identification. Unfortunately, reference barcode libraries of species-rich taxa are often incomplete. In fact, in many insect groups a few common species are overwhelmed by a high number of rare species  (Lim et al. 2011). While common species are likely better represented, rare species are often missing in barcode libraries. This may lead to imbalanced taxon representation. Another critical issue of DNA barcoding is the effect of geographical sampling  (Bergsten et al.
The current dataset presented herein is a result of a pilot study focusing on Old World hybotid diversity. An overall high sequence divergence was observed in our dataset, which is not surprising in the light of the age and diversification pattern of dance flies  (Wiegmann et al. 2003). Although most species could be well distinguished based on a single mitochondrial marker (Figure  1  and Supplementary file 2), we observed several inconsistencies with current classification and extensive overlaps of intra-and interspecific divergences. Our limited sampling of specific and subspecific levels with up to nine samples per species did not allow us to perform extensive tests on barcoding performance and species (or genus) delimitations. We are also aware of the potential pitfalls when analyzing taxonomically incomplete datasets.
Second, large intraspecific distances and low interspecific distances among closely related species may pose a major problem, and even the use of refined criteria such as best close match  (Meier et al. 2006)  or ad hoc thresholds  (Virgilio et al. 2012)  might not solve this issue. Therefore, in datasets where intra-and interspecific divergences largely overlap, using distance-based thresholds alone may not work. In these cases, species or species complexes may have to be analyzed individually and also other DNA markers (including nuclear markers) should be considered for species delimitation and perhaps for revising our ideas about species identification. In the case of recently diverged species, a number of methods have been compared  (van Velzen et al. 2012 ) such as tree-based (Neighbour-Joining or tree-based parsimony), similarity-based (nearest neighbour or BLAST), statistical and diagnostic or character-based (e.
Acknowledgements We thank  Jean-Luc Renneson ,  Marc Pollet ,  Pol Limbourg ,  Alain Drumont (Belgium), Christophe Daugeron (France) ,  Rui Andrade  (Portugal),  Igor Shamshev  and  Semen Kustov  (Russia) and  Adrian Plant  ( United Kingdom ) for their assistance. We also thank three anonymous reviewers for their constructive comments. We appreciate the assistance of  Dinarzarde Raheem  (Belgium), her comments and corrections improved the text significantly. We also thank the  National Parks of Singapore (Singapore)  and the  University of Kisangani  (D. R. Congo). JEMU is financed by the  Belgian Science Policy Office (Belspo).
There are a number of known drug interactions with potent inhibitors and inducers of cytochrome P450 3A4 due to a partial metabolism of rivaroxaban by this cytochrome  (24). Two dose studies, the ODIXa-DVT  (27)  and EINSTEIN-DVT studies  (28) , on the treatment of VTE suggest that the initial treatment of VTE requires more aggressive dosing, whereas a subsequent dose reduction maintains the initial efficacy while decreasing the risk of bleeding. Thus, the optimal dosage regimen used in phase III studies is 15 mg twice daily for 3 weeks followed by long-term treatment with 20 mg once daily  (29). The EINSTEIN program assessed the safety and efficacy of new anticoagulants in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and in long-term thromboprophylaxis. The EINSTEIN-DVT study (clinicaltrials.
gov NCT00440193) found that rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily was effective in the reduction of symptomatic recurrent venous thromboembolism after 6 months of treatment, in addition to the standard treatment regimen including parenterally administered enoxaparin for 5 days followed by a VKA with a target international normalized ratio (INR) of 2. 5. Major and clinically relevant non-major bleeding rates were similar between the two treatment groups (Table  3 )  (24, 30). Results from the recently published EINSTEIN-PE study (clinicaltrials. gov NCT00439777) were similar, with rivaroxaban non-inferiority to standard therapy, at the same regimen, but in the treatment of PE. Major or clinically relevant non-major bleeding composite rates were also similar between the two treatment groups, but major bleeding rates alone, which were defined as secondary outcome, were found significantly inferior for rivaroxaban  (31).
Patients receiving initial antithrombotic therapy for DVT or PE were enrolled in the EINSTEIN-Extension study (clinicaltrials. gov NCT00439725), the results of which showed that rivaroxaban could be used for the long-term secondary prevention of VTE. Nevertheless, the risk of bleeding during long-term anticoagulant therapy should be evaluated carefully. Indeed, this study showed that after 6-12 months of treatment, rivaroxaban at a dose of 20 mg once daily significantly reduced the risk of recurrent VTE at the cost of a moderate increase in clinically relevant non-major bleeding (Table  3 )  (24, 30, 32). Following a pivotal ROCKET AF study (clinicaltrials. gov NCT00403767) rivaroxaban has recently obtained marketing authorisation for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and with one or more risk factor(s), such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke or transient ischaemic attack.
The efficacy and safety of rivaroxaban compared to enoxaparin were investigated for thrombosis prevention in hospitalized medically ill patients in the MAGELLAN program (clinicaltrials. gov NCT00571649). Although this study was completed in 2010, the results have not yet been published. Rivaroxaban was also assessed for the prevention of cardiovascular events in patients with acute coronary syndrome (ACS), with the ATLAS 2 TIMI 51 program following the ATLAS ACS TIMI 46 dose-finding phase II study (Table  5 )  (37).
Apixaban is currently under evaluation for VTE prevention in patients hospitalized for an acute medical illness by the ADOPT phase III study (clinicaltrials. gov NCT00457002) and for VTE prevention in cancer patients by the ADVOCATE phase II study (clinicaltrials. gov NCT00320255). Following the BOTTICELLI DVT doseranging study, a treatment regimen (10 mg apixaban twice daily for 7 days followed by 5 mg twice daily) was selected for investigation in phase III studies  (40). The AMPLIFY study (clinicaltrials. gov NCT00643201), investigating apixaban for the treatment of VTE at a higher dose for the first 7 days, as with rivaroxaban, compared to conventional therapy (LMWH followed by VKA), is underway. In the AMPLIFY-EXTENSION study (clinicaltrials. gov NCT00633893), apixaban 2. 5 mg or 5 mg twice daily is compared to placebo for the secondary prevention of VTE.
Lower rates of bleeding and mortality were reported (Table  4 ). Indeed, the new anticoagulant reduces the risk of stroke or systemic embolism by 21%, major bleeding by 31%, and death by 11% compared to warfarin. Apixaban would prevent a haemorrhagic stroke in 4 patients per 1000 and an ischaemic or unknown type of stroke in 2 patients per 1000  (42). In the ongoing AVERROES study (clinicaltrials. gov NCT00496769), apixaban 5 mg twice a day (or 2. 5 mg twice daily in selected patients) seems promising for the prevention of stroke and systemic embolism in AF and demonstrates superior efficacy compared to acetylsalicylic acid (81-324 mg once daily). Indeed, apixaban substantially reduces risk of stroke or systemic embolism with no significant increase in major bleeding rates (Table  4 ). It presents fewer serious side effects and lower rates of discontinuation of medication compared with aspirin.
Betrixaban (PRT 054021, Portola Pharmaceuticals) at doses of 15 mg and 40 mg twice daily showed an effective antithrombotic action and was well tolerated by patients during the EXPERT phase II study ongoing in the US and Canada for the prevention of VTE after orthopaedic surgery for total knee replacement (Table  6 )  (45). The efficacy and safety of this new anticoagulant have not yet been evaluated in phase III trials. The results of the EXPLORE-Xa doseranging study (clinicaltrials. gov NCT00742859) investigating betrixaban for stroke prevention in patients with non-valvular AF are not yet available (Table  4 ).
Edoxaban Edoxaban (DU-176b, Daiichi Sankyo), another oral direct factor Xa inhibitor, is currently under investigation for the prevention and treatment of VTE and for the prevention of systemic thromboembolism in AF. The effectiveness of edoxaban as thromboprophylaxis for major orthopaedic surgery has been established in phase III studies (Table  6 ): for total knee replacement (STARS E-3, clinicaltrials. gov NCT01181102), total hip replacement (J-STARS 5, clinicaltrials. gov NCT01181167) and hip fracture surgery (J-STARS 4 clinicaltrials. gov NCT01181141). Edoxaban at a dose of 30 mg once daily was compared to enoxaparin 20 mg twice daily and showed a significant reduction in venous thromboembolic events with no difference in major bleeding rates between treatment groups  (46). The HOKUSAI-VTE study (clinicaltrials.
gov NCT00986154) is designed to investigate the efficacy and safety of edoxaban for the initial treatment of VTE. There is no specific dose study, therefore it is not possible to speculate on a higher dosage during the first days of treatment followed by a subsequent dosage reduction, as for rivaroxaban and apixaban. In the phase III study, edoxaban 60 mg once daily is administered after initial parenteral anticoagulant therapy and this is compared to initial parenteral treatment followed by VKA (Table  3 )  (14). The ENGAGE-AFTIMI-48 phase III study (clinicaltrials. gov NCT00781391) (47) is designed to compare edoxaban with warfarin for the prevention of thromboembolism in patients with AF. This study follows the dose-finding study (clinicaltrials. gov NCT00504556)  (48) , in which edoxaban 30 mg or 60 mg once daily showed a favorable side-effect profile in terms of efficacy and safety (Table  4 ).
Darexaban A number of phase II and III studies (clinicaltrials. gov NCT00353678, NCT00913120, NCT00902928) investigate darexaban (YM150, Astellas Pharma) in VTE prevention after hip arthroplasty  (49) (50) (51)  and evaluate the superiority of the new anticoagulant over enoxaparin (PEARL-1, clinicaltrials. gov NCT00408239), warfarin (PEARL, clinicaltrials. gov NCT00595426) and placebo (clinicaltrials. gov NCT00917254) in thromboprophylaxis after knee arthroplasty (Table  6 ). Darexaban is also evaluated for the treatment of DVT and PE (clinicaltrials. gov NCT00937820) (Table  3 ), for the prevention of VTE in hospitalized medically ill patients (clinicaltrials. gov NCT01028950), after a hip fracture (clinicaltrials. gov NCT00937911) and after major abdominal surgery (clinicaltrials. gov NCT00942435).
Two phase II studies were designed to investigate an antithrombotic effect of the new drug in stroke prevention in patients with AF (clinicaltrials. gov NCT00448214 and OPAL-2, clinicaltrials. gov NCT00938730) (Table  4 ). Results were only published as abstracts  (52, 53). The RUBY-1 study (clinicaltrials. gov NCT00994292) evaluated darexaban in combination with dual antiplatelet therapy for the secondary prevention of ischemic vascular events after ACS. It found a two-to four-fold increase in major and clinically relevant non-major bleeding, with no significant increase in efficacy compared to placebo (Table  5 ). On the other hand, darexaban was well tolerated, with no signs of hepatotoxicity. A large phase III trial is required to demonstrate the potential of low-dose darexaban to prevent major cardiac events after ACS  (54).
TAK-442 Two dose-finding studies investigated the efficacy, safety and tolerability of TAK-442 (Takeda) in the prevention of VTE after total knee replacement and in the secondary prevention of ischemic vascular events in patients with ACS. In the first study (clinicaltrials. gov NCT00641732) recruitment was stopped early in the groups receiving TAK-442 at doses of 10 mg or 20 mg twice daily due to a high rate of DVT, EP or allcause mortality compared to control group. The efficacy and safety profiles of other doses were similar to enoxaparin (Table  6 )  (55). In the second study (clinicaltrials. gov NCT00677053), 8 dosage regimens of TAK-442 in combination with standard antiplatelet therapy were evaluated in terms of efficacy and safety versus placebo (Table  5 ). The results of this study are not yet available.
LY517717 In the phase II study (clinicaltrials. gov NCT00074828) LY517717 (Lilly), difumarate at doses of 100, 125 and 150 mg demonstrated noninferior efficacy and similar bleeding rates compared to enoxaparin in the prevention of venous thromboembolic events after orthopaedic surgery of the lower limbs (hip or knee replacement) (Table  6 )  (56). No information on the future development of this drug is available.
Otamixaban Otamixaban (XRP0673, Sanofi-Aventis) is a novel intravenous short-acting direct FXa inhibitor that can be used in acute situations. Initially evaluated in non-urgent percutaneous coronary intervention (SEPIA-PCI clinicaltrials. gov NCT00133731), this drug showed promising results in terms of efficacy and safety  (57). In the SEPIA-ACS1 TIMI 42 phase II study, otamixaban was investigated in patients with non-ST-segment elevation acute coronary syndromes and requiring revascularisation versus conventional anticoagulant (UFH) and antiplatelet (glycoprotein IIb/IIIa inhibitor) therapies  (58). Administering eptifibatide before and during percutaneous coronary intervention in patients with unstable angina was found to significantly reduce the risk of death and myocardial infarction  (59, 60).