dataesr/scientific-paragraphs-categorization huggingface dataset:
Study limitations Our study had several limitations that may have affected the results and analysis. Firstly, there was only a small number of children in the study and also a considerably lower number of H. influenzae infections than pneumococcal infections. Secondly, some data were only recorded in the medical charts as recurrent infections, which may have led to an underestimation of their actual rate. Thirdly, early and late determination of the Ig levels may have affected the Ig values as discussed below. The cut-off levels we used to define the Ig abnormality are a matter of debate. No data exist to certify a threshold under which an infectious risk exists. Therefore most authors have used laboratory values to assess normality, with 'abnormal' values less than 6 g/l for IgG, 0. 7 g/l for IgA, and 0.
5 g/l for IgM. We used artificial cut-off levels similar or lower to those provided by our laboratory or the literature. Immunoglobulin determination is a simple and broadly available test. The quality of the immune response as determined by the pneumococcal polysaccharide antibody measurement would be of interest to explore, as an adapted immune response may compensate for an inadequate Ig level. However, these techniques can be difficult to perform and therefore are considered as second-line tests for exploring humoral deficiencies. 10 We did not include IgG subclasses in our study as their interpretation and management are difficult and, similar to pneumococcal polysaccharide antibody determination, are regarded as second-line examinations. 10 Half of the Ig measurements were carried out within 4 days of invasive disease, although a few patients had considerably later measurements (0-214 days) due to long hospitalizations, with a change of ward allowing new Ig assays when the data were missing.
Overall study design This study was a phase II, randomized, double-blind, multicenter clinical trial examining the safety and immune responses of TNF-K in adults with RA who previously experienced a secondary failure of anti-TNF biologics (ClinicalTrials. gov registry no. NCT01040715). The primary objective was to identify the best dose and schedule of administration of TNF-K in terms of anti-TNF antibody response induced by either 2 injections (day 0 and 28) or three injections (day 0, 7, and 28) of TNF-K at 3 dosages (90, 180, or 360 mg). Patients gave written informed consent before inclusion in the trial. The protocol for this trial and supporting CONSORT checklist are available as supporting information; see S1 Checklist and S1 Protocol.
The placebo was an equivalent amount of stabilizer (mannitol) in 0. 3 mL water and emulsified with an equal volume of the adjuvant ISA-51VG. Both TNF-K and placebo were supplied as white cake in identical numbered vials so that the patient and investigator were blinded to the treatment administered. Doses were injected intramuscularly into the deltoid area of the arm. Treatments were randomly assigned using a sequential, incremental, staggereddose design (Fig. 1 ). In each stage, patients were also randomized to the study arm and 1:1 to receive 2 doses (day 0, 28) or 3 doses (day 0, 7, 28). Randomization was via a central interactive web response system, using a randomization list generated with SAS (SAS Institute, Cary, NC). For stages 1 and 2, after 3 patients had been enrolled since at least 7 days and if no safety issue was detected by an independent DSMB (iDSMB) and no related Serious Adverse Event was reported, enrolment in the subsequent stage started in parallel.
Methods and Data Collected Cambodia ranks amongst the 42 countries with the highest prevalence of wasting worldwide, with wasting implicated in more than 6,400 child deaths annually  [7]. To advise the Ministry of Health of Cambodia on the most effective strategy to identify children with SAM, we assessed the sensitivity and specificity of MUAC on detecting children with a WHZ,23, using data from 4 recent surveys conducted in Cambodia between 2011 and 2013. Though other cut-offs for MUAC such as ,125 mm and , 135 mm have been suggested to detect SAM  [8] , these alternative cut-offs have not been validated at a sufficiently large scale in the literature. Therefore, our objective was to determine the optimal cut-off for MUAC to detect children with either SAM or MAM, considering that even though a MUAC cut-off of 115 mm alone is currently the criteria recommended by WHO to identify SAM at community level, WHZ,23 is still considered the golden standard to identify SAM in children under 5 years of age.
Data on weight, height, MUAC and age were available for a total of 11,818 children, from 4 different surveys conducted by several organizations (UNICEF, WHO, WFP, World Vision and International Relief and Development) between 2011 and 2013. The target population was children aged 0-59 months. Measurements of MUAC (to the nearest 1 mm) were made using a nonstretch tape measure (provided through UNICEF). Weight was measured with the child wearing no clothes, or only light clothes, and was recorded to the nearest 0. 1 kg by a Salter scales. Length/ height was measured to the nearest 0. 1 cm with a ''Holtain infantometer''. Age was determined (calculated in the nearest months) by asking of both the child's age and date of birth. All data were entered into PASW statistics 18 (Chicago, USA). Anthropometric data was transformed to Z-scores using WHO Anthro (version 3.
This will identify, according to our data set, over 65% of the children with a WHZ,23. Then, as a second step, all children with a MUAC below the screening cut-off (e. g. , 133 mm) should be assessed at a secondary facility, e. g. a primary health care center, for weight, height and MUAC measurements. Subsequently, malnutrition can be diagnosed as SAM using both MUAC (now at diagnostic cut-off: ,115 mm) and WHZ (,23) criteria independently of each other. Such an approach will not only solve the current confusion and conflicting findings, but also improve the cost-effectiveness of screening programs and the treatment because sensitivity will be significantly improved. Although in this Cambodian data set, a MUAC of 133 mm was optimal, a wider consensus should be reached on a global, ideal cut-off, taking not only feasibility into account, but also specificity.
Having a high number of false-positive cases, could lead to many children visiting health center being turned away without  intervention, undermining confidence in the health system. Moreover, MUAC was highly dependent on age in our dataset, and increased especially after 2 years of age (data not shown). Hence, age-specific cut-offs for MUAC might have a higher sensitivity than a single cut-off, although this could complicate community-level screening. But as clearly shown in Figure  4 , as single cut-off for MUAC in children between 6 and 59 months would tend to overestimate the prevalence of malnutrition in younger children, especially younger girls, and underestimate the prevalence of malnutrition in older children, especially boys. For countries with a policy for screening and treating of also moderate acute malnutrition, the same rationale prevails.
A similar two-step screening procedure should be applied, with community screening using a MUAC,138 mm (optimal cut-off in Cambodain data set), and consequent secondary diagnostic followup at a primary health center using a treatment criteria of MUAC,125 mm or WHZ,22. Community screening by MUAC,138 mm will, according to our data set, identify over 75% of the children with a WHZ,22. Indeed, as over 80% of children with WHZ,23 are identified by a MUAC,138 mm, it could be argued that for simplicity, one cut-off for community screening for wasting (combining MAM and SAM), using MUAC,138 mm would suffice, although this would double the false-positive rate (from 13% to 28%). As highlighted in the updated WHO guidelines for management of SAM  [3] , several research priorities remain, including refinement of the current cut-off values for MUAC for children at different age ranges, such as those below 6 months and.
1] [12] [13] [14] [15]  In addition, a laboratory school study in children and a simulated workplace study in adults showed that the effects of LDX were ongoing at 13 and 14 hours (these being the last time points evaluated), respectively. 15, 16 The present investigation (SPD489-326; ClinicalTrials. gov Identifier NCT00784654) was preceded by a 7-week, phase 3 European trial (SPD489-325; ClinicalTrials. gov Identifier: NCT00763971) in 336 children and adolescents with ADHD, which found that both LDX and the reference treatment OROS-MPH produced significantly greater improvements than placebo in symptoms and global improvement, as assessed using the ADHD-RS-IV and Clinical Global Impressions-Improvement (CGI-I), respectively. 13 Adverse events associated with LDX treatment were consistent with the known effects of long-acting stimulant use.
Written informed consent was provided by each patient's parent or legally authorized representative, and documentation of assent (if applicable) by the patient was required to confirm that he or she was aware of the investigational nature of the study and the required procedures and restrictions in accordance with the ICH GCP Guideline E6 and applicable regulations. The study protocol and amendments (http:// clinicaltrials. gov/ct2/show/NCT00784654) were approved by the institutional review board or independent ethics committee of each center.
Statistical Analysis The primary efficacy analysis was performed on the percentage of patients meeting treatment failure criteria by the end of the RWP using the Cochran-Mantel-Haenszel (CMH) test stratified by country. RWP endpoint was the last on-treatment visit after randomization (visit 3R) with a nonmissing assessment. Patients who withdrew from the study during the RWP and did not provide efficacy data at the early termination visit were classed as treatment failures, as were those without an endpoint value. Treatment failure rates during the RWP were also assessed using the CMH test at each double-blind visit. The difference between groups in time to treatment failure (days) was assessed using the Wilcoxon test, stratified by country. Mean changes from baseline in ADHD-RS-IV scores during the OLP were assessed using a 1-sample t test.
Results Serological data were available for 315 women at the beginning of pregnancy, 255 in north and 60 in southeast France. The overall HEV prevalence was 7. 74% (CI 4. 7%-10. 8%). Seroprevalence was higher in south than in north: 29. 3% (CI 15. 3%-43. 2%) vs. 3. 6% (CI 1. 3%-5. 9%). Women with detectable IgG by the Wantai assay were older: 32. 5+/-5 vs. 29. 4+/-5 years (p = 0. 012). No IgM positivity was detected in early pregnancy. Postpartum serology was available for 140 women (44. 4%), in an average of 6. 4+/-1. 7 months' interval after initial sampling. No IgG seroconversion or IgM detection were observed in this second sampling. Completed questionnaires were available at the beginning of the pregnancy in 188 cases (59. 6%). No difference was observed between women with and without IgG regarding trips abroad (p = 0.
Introduction The first DNA genome to be completely sequenced belonged to the diminutive single-stranded DNA (ssDNA) phage jX174, initiating the genomic sequencing era in 1977  (Sanger et al. , 1977). Knowledge of phage biology and ecology has expanded rapidly since that time, and phages are currently recognized as the most abundant biological entities on the planet, exerting significant driving forces on bacterial diversity and global biogeochemistry  (Breitbart, 2012). Despite the early characterization of ssDNA phages, their doublestranded DNA (dsDNA) counterparts have received a disproportionate amount of attention over the past three decades. As of 2011, 480% of the completely sequenced phage genomes in Genbank belonged to tailed dsDNA phages of the Caudovirales  (Krupovic et al. , 2011).
Sample collection, processing and DNA extraction Samples from 10 different sites were examined: six in Florida, USA, and four from the Antarctic shelf. Several methods were used to purify viruses and concentrate DNA from these environmental samples, which were mostly samples of opportunity prepared for other projects. Surface water samples were collected in August 2012 from Wall Springs (freshwater (FW); 100 l), Wall Estuary (saline (SW); 100 l) and Bayboro Harbor (SW; 200 l). GPS coordinates, salinity and temperature data are recorded in Table  1. Water was strained through 100 mm Nitex mesh, then concentrated down to B100 ml using a 100 kD tangential flow filter (GE Healthcare, Pittsburg, PA, USA) as described previously  (Thurber et al. , 2009). The retentate was filtered through a 0. 22 mm Sterivex filter (Millipore, Billerica, MA, USA) to remove bacteria and larger cells.
Sequence analysis Sequences were trimmed for quality and vector removal using Sequencher (Gene Codes, Ann Arbor, MI, USA). Trimmed sequences were compared against the Genbank non-redundant (nr) database Sequences with BLASTX similarity to Microviridae were dereplicated at the 97% nucleotide level using FastGroup II  (Yu et al. , 2006) , which was also used to compute the Shannon-Weiner Diversity Index  (Shannon and Weaver, 1949). The sequences were provisionally translated into amino-acid format and aligned using the ClustalW algorithm in MEGA5 with subsequent manual adjustment  (Tamura et al. , 2011). After obtaining optimal amino-acid alignment, the alignment was back-toggled and exported for phylogenetic construction. The phylogeny in Figure  2  was generated using the PhyML package  (Guindon et al.
, 2010) ; a maximum-likelihood method employing the GTR model with support values determined by approximate likelihood-ratio test  (Anisimova and Gascuel, 2006). The phylogeny in Figure  3  is a maximum-likelihood tree generated in the FastTree package  (Price et al. , 2009)  using the Whelan-and-Goldman residue model from a maximum-likelihood training 'intree' generated in MEGA5 from a ClustalW alignment  (Tamura et al. , 2011). The clade-based hidden Markov models combined in Supplementary Figure  1  were calculated using 'hmmbuild' within the HMMER3. 0 package  (Eddy, 2008).
Homology modeling of gokushoviruses Structural models of gokushovirus MCPs were built using the homology model-building package MODELER  (Yang et al. , 2012). The full-length MCP sequences of the reference 'seed' gokushoviruses (six Chlamydia phages, SARssf1&2, BdfMH2k) were aligned against the MCP of Microviridae with available structures (fX174, Bacteriophage alpha-3, G4, SpV4) using CLUSTAL-W2  (Larkin et al. , 2007). Presence of large insertions (480 amino acids) at the threefold loop region as seen in SpV4 prompted use of the pseudo-atomic model of SpV4 instead of the higher resolution coliphage (fX174, a3 and G4) models as the primary template for model building. Superposition of the homology models was carried out in the COOT package  (Emsley et al. , 2010). The online server, VIPERdb2  (Carrillo-Tripp et al.
, 2000)  as well as many other viral families with T ¼ 1 capsids  (McKenna et al. , 1992; Agbandje-McKenna and Kleinschmidt, 2011). Gokushovirus MCPs were recovered from all environments tested (freshwater, estuarine, sediments, sewage). A total of 537 sequences were retained following BLASTX parsing, which were then dereplicated within each sample at 97% identity with gaps, yielding 315 sequences for downstream analyses (Genbank Accession No. KF689226-KF689540), which are represented in Figure  2  phylogeny. Notably, the average size of the aligned amplicons from the environmental samples was 636±22 nt, compared with 705±32 nt in the Chlamydia phages. The difference in length between environmental and cultured gokushoviruses was largely driven by differences in the length of the threefold loop; in the Chlamydia phages the loopcoding region had an average length of 230 ± 23 nt, whereas in the environmental samples the same region averaged 166±19 nt.
The smaller size of environmental phage amplicons as compared with cultured isolates has also been reported for dsDNA phages  (Breitbart et al. , 2004) , although the reason for this discrepancy is unknown. A capsid homology model was generated to examine the amplicon from a structural perspective. High-resolution crystal structures with B3-3. 5 A resolution are available for bacteriophages fX174 (PDB ID: 1AL0), a3 (PDB ID: 1M06) and G4 (PDB ID: 1GFF), which are all members of the enterobacteria-infecting 'true' Microvirus genus (family Microviridae). Structures of 'true' Microvirus capsids by X-ray crystallography revealed spike ('G'), DNA-pilot ('H') and DNA-binding ('J') proteins, in addition to major capsid proteins ('F')  (Dokland et al. , 1997). However, the nucleotide-level sequence identity of the MCPs of the nine reference gokushoviruses to those structurally resolved 'true' microviruses only ranged between 18 and 20%.
, 2012; Brum et al. , 2013; Labonteand Suttle, 2013) , this study emphasizes the need for a shift in the paradigm that dsDNA Caudovirales dominate environmental viral communities. National Science Foundation; SR was supported by a PhD grant from the French Defense Procurement Agency (DGA); AS was funded by NSF ANT-1246378. Thanks to the members of the British Services Antarctic Expedition 2012 for collecting the Marguerite Bay marine sediment samples and to Dawn Goldsmith and Bhakti Dwivedi for assistance with bioinformatics and primer design, respectively.
Acknowledgements Funding for this study was provided by grants to MB from the  National Science Foundation  (Microbial Interactions and Processes  MCB-0701984  and  Division of Biological Infrastructure   DBI-0850206 ) and a  Proposal Enhancement Grant  from the  University of South Florida Internal Awards Program. MAM and SK were funded by  University of Florida COM Research Funds ; MH was funded by a  Presidential Fellowship  from the  University of South Florida ; AC was funded by an  REU Supplement  from the.
Acknowledgments This project was partially funded by  University of Malta  under the  University Research Scheme  ( PHBRP08-03  and  PHBIN26-01 ) and  EU COST Action   CM1103  " Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain " and  Fondo Finalizzato alla Ricerca  (FFR) 2012 ex  60% ,  Universita' di Palermo. We are grateful to  Arena Pharmaceuticals ,  San Diego ,  United States  ( Dr Andrew J Grottick , Senior Director,  CNS Drug Discovery)  for the kind gift of a sample of lorcaserin.
© 2014 Ratbi et al. ; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4. 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1. 0/) applies to the data made available in this article, unless otherwise stated. Ratbi et al. Journal of Medical Case Reports 2014, 8:471 http://www. jmedicalcasereports. com/content/8/1/471.
Adverse Events Any adverse events (AEs) that occurred during the period from administration of the first dose (day 1) to the follow-up visit (1 week AE 3 days after the last dose of study drug intake) were reported, whether or not the event was considered to be treatment related. No protocol-specific laboratory values were collected. Any routine laboratory values considered by the investigator to indicate a clinically significant deviation were reported as AEs. An independent Data and Safety Monitoring Board assessed unblinded safety data in regular intervals during the study.
Methodology for Statistical Analysis The number of patients in the individual studies was chosen to ensure 90% power in demonstrating an improvement in total fat absorption assuming a true difference of 10 percentage points and a common standard deviation of 15 percentage points  (18). Neither of the studies was expected to have sufficient power to demonstrate an improvement in growth, because of the relatively small number of infants in each study; therefore, a predefined analysis of combined Formula + rhBSSL 0. data from the 2 studies was specified, ensuring 80% power in demonstrating improvement in growth assuming a true difference in growth velocity of 2 g Á kg À1 Á day À1 for rhBSSL treatment over placebo. The statistical analysis plan detailing the analysis of combined data was developed and finalized before database lock and unblinding of the clinical database for either of the 2 clinical studies.
Study Population Patient Disposition A total of 65 preterm infants were randomized across the 2 clinical studies: 33 infants in the PF study and 32 infants in the PBM study. The number of infants completing and discontinuing during the treatment periods, and the reasons for discontinuation, are shown in Figure  2. In total, 63 infants received at least 1 dose of study treatment and were evaluated for safety (safety analysis set) (Table  2 ). Sixty infants, who received at least 1 dose of the randomized study medication and had 1 baseline and at least 1 postbaseline weight assessment in both treatment periods, were evaluated for clinical efficacy (full analysis set, FAS). The CFA analysis was conducted based on data from the 46 infants for whom complete data on food intake and full stool collections during the required period were available (per-protocol [PP] analysis set).
CFA Fat Intake As part of the CFA analysis, the total amount of fat ingested between GI transit markers was estimated, together with the total amount of fat in the stools during the same period. The amount of fat ingested was similar during the rhBSSL and placebo treatments; the Ã Infants who received at least 1 dose (rhBSSL/placebo). y Infants who received at least 1 dose (rhBSSL/placebo) and had a baseline and at least 1 postbaseline weight assessment in both treatment periods. z Infants for which complete data on food intake and stool collections were available. mean fat intake in the 72-hour fat-balance period during rhBSSL treatment was 4. 84 g Á kg À1 Á day À1 compared with 4. 92 g Á kg À1 Á day À1 for placebo (Table  5 ); however, there was a pronounced difference in fat intake between infants receiving formula and PBM; those fed with formula received 5.
In addition, rhBSSL improves the absorption of the clinically important LCPUFAs ARA and DHA, which are important factors for healthy infant development. rhBSSL had an AE profile similar to placebo. Because the encouraging phase II results of short-term treatment with rhBSSL presented here warrant confirmatory studies, a randomized placebo-controlled phase III study with 4-week treatment in preterm infants is ongoing (http://clinical trials. gov/ NCT01413581). If an infant had >1 count for a particular preferred AE term, the infant was counted only once in any treatment period. AE ¼ adverse event; rhBSSL ¼ recombinant human bile salt-stimulated lipase.
Acknowledgments: The authors thank the following investigators for their major contributions in the 2 double-blind clinical trials: Italy,  Maria Paola Bellagamba  (Ancona);  Costantino Romagnoli ,  Simonetta Costa ,  Mario De Curtis , and  Lucilla Managanozzi  (Rome);  Lino Chiandetti  and  Giovanna Verlato  (Padua);  Nicola Laforgia  and  Grazia Calderoni (Bari); France, Elsa Kermorvant (Paris) ;  Umberto Simeoni ,  Veronique Millet , and  Farid Boubred (Marseille) ;  Elie Saliba  and  Amelie Favreau (Tours) ;  Nathalie Montjaux  (Toulouse). We also acknowledge  Maria Rodrı ´guez Palmero ,  Ordesa, Spain , for providing the preterm infant formula, and the assistance of a medical writer,  Josie Saulter , for the initial drafting of the manuscript. Last but not least, we sincerely thank the families who consented to their preterm infants being included in these studies.