(b) Box and whisker plots showing range … Taxonomic Diversity The taxonomic diversity of sequenced marine phages is quite low as compared to the diversity of the sequenced selleck inhibitor phages from all habitats (Figure 6). Of the 27 marine phages sequenced, all are double-stranded DNA phages, with no RNA stage; 96% are of the viral order Caudovirales (Pseudoalteromonas phage PM2 has an unclassified order and belongs to the Corticoviridae family), as opposed to 76% of all sequenced phages (123 phages with no order span 13 different Classes). Figure 6 Overview of phage taxonomic data. (a)The taxonomic distribution of all sequenced phages versus all sequenced marine phages and (b) the hosts of all sequenced marine phages. All information describing marine phages and their hosts is accessible via GCDML ..
. Among all sequenced phages, there is general bias towards double-stranded DNA (dsDNA) viruses lacking an RNA stage (possibly influenced by, e.g., cloning biases in sequencing efforts, chloroform extractions that disrupt lipid-membranes of, i.e., dsRNA viruses, the difficulty in culturing archaeal hosts, etc.), despite the fact that, from an epidemiological perspective, over 75% of all viral diseases are the result of RNA viruses , which are yet to be represented by any sequenced marine phage isolates. The odd dsRNA phages have segmented genomes, whereby multiple ‘chromosomes’ exist in each virion and are often re-assorted during co-infection of the same host , where phages can exist in a ‘carrier state’, reproducing without killing their host .
This feature, combined with the intrinsic low fidelity of RNA replication, allows for RNA viruses to rapidly adapt to new environments, offering insights into modeling of viral population genetics and evolutionary theory that we can not yet consider in the marine realm . ssDNA phages are also one of the major ‘odd’ phages groups not yet represented in the marine phage genome collection (Panel a Brefeldin_A of Figure 6), and are also under selective pressure quite unique from their dsDNA counterparts . Distribution of hosts The distribution of their hosts is also biased (Figures 4 and and5).5). Two thirds of the sequenced marine phages infect Proteobacteria. Furthermore, most hosts are restricted to three major sets; 30% infect Vibrio spp., 33% infect Cyanobacteria (either Chroococcales or Prochlorales), and another 30% infect Alphaproteobacteria (all but one infect Rhodobacterales) (Panel b of Figure 6). All sequenced marine phages infect only two of the twenty-four Bacteria phyla (Proteobacteria and Cyanobacteria) and no Archaea (Panel b of Figure 6).
arsenaticum. Table 6 Summary of genome: one chromosome and one extra-chromosomal element Table 7 Genomic inversions present within the sampled population The majority of the P. oguniense genome is structurally syntenic to the genome of P. arsenaticum, and genes found in both species show an average of approximately selleck products 96% nucleotide identity. The P. oguniense genome is approximately 15% larger than P. arsenaticum, with the former encoding 536 more (2835 – 2299) open reading frames (ORFs) predicted to be genes. Vast stretches of sequence space are syntenic between the two species (Figure 2, regions in blue), broken by relatively few regions that appear to arise from either gene loss in P. arsenaticum or genomic expansion in P. oguniense, possibly a result of the numerous paREP elements present in these genomes (Figure 2).
These repetitive regions are difficult to assemble, and some are putative transposons (PaREP2b, for example). Figure 2 Genomic alignment of P. oguniense with P. arsenaticum. Outer ring: P. oguniense (+ strand); Inner ring: P. arsenaticum (- strand). Inter-species alignment blocks shown in light blue and gold (inverted orientation). Intra-species P. oguniense genomic inversions … We can identify specific genes and gene clusters that are present in P. oguniense but are missing in P. arsenaticum. Notably, the cobalamin synthetic cluster and two thiamine synthetic genes (ThiW and ThiC) are absent in P. arsenaticum. The terminal cytochrome cluster associated with aerobic respiration  is also absent in P. arsenaticum as expected from an obligate anaerobe.
Among the 16 largest deletions in P. arsenaticum (relative to P. oguniense), four are associated with paREP2 genes, six with paREP1/8, and one with paREP6 (Table 5). Conclusion Genomic sequencing and assembly of Pyrobaculum oguniense has yielded a complete genome and an extra-chromosomal element. The main chromosome is largely syntenic to Pyrobaculum arsenaticum and contains a number of gene clusters that are absent in that species. This is of particular interest considering that these species were isolated on opposite sides of the Eurasian continent; P. oguniense was isolated in Japan, while P. arsenaticum was isolated in an arsenic-rich anaerobic pool in Italy. The synteny that has been retained between the genomes of P. oguniense and P.
arsenaticum allows a close examination of gene gain or loss events in the genetic history of these two species. P. arsenaticum is missing the gene clusters that support cobalamin and thiamine synthesis, and it is missing the aerobic cytochrome cluster. Given that P. oguniense and the next closest member in the clade, P. aerophilum, have both retained these capabilities; Drug_discovery the most parsimonious explanation is gene loss in P. arsenaticum. Because these genes are located at disparate positions in the P.
As 2011 draws to an end and we close out the final issue of Volume selleckchem Belinostat 5 of SIGS, we thought it appropriate to provide our authors, reviewers and readers with a brief update on the ��state of the journal��, to examine the evidence that supports our original idea for the need for a journal such as SIGS, and to briefly outline key plans for the future. Milestones One of the significant hurdles for any new publication is acceptance by potential authors and readers. Authors must be willing to take the risk of contributing articles to an untested journal and readers must be willing to take a risk reading and citing those articles in their own work. We have been fortunate in that SIGS became a primary outlet for articles derived from the Genomic Encyclopedia of Bacteria and Archaea (GEBA) .
Early on it became obvious that our highly structured and standardized Short Genome Report format was well suited for the project, as it would allow comparison of descriptive information about the genomes and the source organisms. In addition, adherence to the same format for genomes derived from other sequencing projects meant that readers could easily place genomes into a consistent and predictable framework. Similarly, reviewers could easily process manuscripts and spot discrepancies that might otherwise go unnoticed. The format has proven to be quite successful and in February 2011, the 100th Short Genome Report was published in SIGS. An additional 50 Short Genome Reports were published by the end of the year. To date, all but one  of the Short Genome Reports was for a bacterial or archaeal genomes.
The taxonomic coverage of the Short Genome Reports published to date is presented in Table 1. Thus far, Short Genome Reports have been published for species or subspecies belonging to 16 of the 32 phyla containing types bearing validly published names. Table 1 Sequenced bBacterial and archaeal type strains having sequenced genomes with and a companion publication To better gauge progress of sequencing efforts in general, a new type of article was introduced in May 2011; a listing of genomes published outside of SIGS. The rationale for this article is to provide the community with a regularly updated list of sequenced genomes for which companion articles have been published. We were able to identify 397 of these articles that were published in 18 journals [8-11].
Excluding the genome sequences of viruses and eukaryotes, the taxonomic coverage of those papers differed somewhat from those published in SIGS, presumably because of the design of the GEBA project, which has focused on the genomes of taxonomic type strains available from public culture collections to Cilengitide maximize diversity. Nonetheless, the total number of genome articles remains relatively low (approximately 1,550) compared to the number of genome sequencing projects that either have been completed or are currently underway (11,221; GOLD).
05) and 247-fold (p<0.01), respectively (Figure 1A). The difference sellekchem in the PRLr mRNA synthesized between 2 and 4 h was significant (p<0.01) as well. The expression of PRL mRNA increased 80-fold (p<0.05) and 133-fold (p<0.01) after 1 and 2 h of LPS stimulation, respectively. Then, PRL mRNA decreased below 30-fold (p<0.01) at 4 h, increased 80-fold (p<0.05) at 8 h, and again decreased below 30-fold after 48 h (p< 0.05) (Figure 1B). Figure 1 PRLr mRNA and PRL mRNA synthesis in THP-1 monocytes activated with LPS using real-time PCR. THP-1 monocytes stimulated with LPS 1 ��g/ml were harvested at different times and three independent RT-PCR experiments were analyzed using comparative ... PRLr and PRL were expressed in THP-1 monocytes stimulated with LPS Two PRLr isoforms of 100 and 50 kDa were identified in THP-1 monocytes by Western blot until 8 h of stimulation with LPS (Figure 2A).
In relation to untreated cells, the expression of the 100 kDa isoform increased from 1 to 8 h, except at 4 h when the expression was significantly lower in comparison with any time after stimulation with LPS (p<0.01) (Figure 2A). A basal expression of the PRLr isoform of 50 kDa was observed (Figure 2A), but an increase in a time-dependent manner was found from 4 h (p<0.05) to 72 h (p<0.01) after LPS stimulation (Figure 2A). Also, a continuous increased expression of PRL of 60 kDa in THP-1 monocytes was detected from 1 to 8 h after stimulation with LPS; then, after 48 h the expression of a bigger PRL of 80 kDa was detected (Figure 2B). No basal expression of PRL was detected in untreated cells (Figure 2B).
Figure 2 PRLr and PRL expression in THP-1 monocytes activated with LPS using Western blot. THP-1 monocytes stimulated with LPS 1 ��g/ml were harvested at different times and two independent Western blot experiments were performed and analyzed using densitometry … Isoforms of PRLr and PRL were expressed by monocytes from healthy subjects after stimulation Cilengitide with LPS In untreated monocytes obtained from healthy subjects a PRLr isoform of 50 kDa (Figure 3A) and PRL of 60 kDa and 23 kDa were found (Figure 3B). Until 8 h after stimulation with LPS, the increased expression of PRLr isoforms of 50 kDa (p<0.05) and 100 kDa (p<0.001) (Figure 3A) and PRL of 60 kDa (p<0.01) was observed, as well as, the decrease of PRL of 23 kDa (p<0.01) (Figure 3B). After 48 hours of stimulation with LPS the increased expression of PRLr isoforms of 100, 90, 65 and 50 kDa (Figure 3A), and the increase of the 80 kD PRL (p<0.001) was revealed, as well as a decrease of PRL of 60 kDa (Figure 3B). PRL of 23 kDa was not detected after 8 h of stimulation with LPS (Figure 3B).
The first laparoscopic cholecystectomy was performed by M��he  however his approach did not become popular until both French MEK162 price and American groups popularized the four-port technique in the early 1990s. The idea of minimally invasive surgery for the removal of the gallbladder had now become a plausible technique that was rapidly accepted as the standard-of-care. Patients quickly learned of the new procedure and began to request it on the basis of a shorter hospital stay, less pain, and smaller scars . The possibility of performing laparoscopic cholangiography, common bile duct exploration, and choledochotomy expanded the role of laparoscopic surgery in the treatment of biliary disease  and further advanced the idea of minimally invasive surgery as the gold-standard for surgery of the biliary tract.
Recently the development of natural orifice transluminal endoscopic surgery (NOTES) opened the field of incision-less surgery. The main goal of NOTES is to eliminate the need for skin incisions along with other theoretical advantages which include: decreased postoperative pain, performing procedures in the out-patient setting, reduced incidence of hernias, reduced hospital stay, and increased overall patient satisfaction [5, 7]. The idea of accessing internal organs through the wall of the vagina, colon, stomach, bladder, and so forth, with the use of rigid or flexible instruments is an attractive one. However, the challenge of obtaining a clean access site thereby preventing intra-abdominal spillage or infection from the incision has not been able to be fully avoided .
Additionally the concern over closure of the luminal incision and the lack of a single effective closure technique for stomach, esophagus, or colon, so far limits the application of this technique. Moreover, the possibility of generating bowel-overdistention due to the pneumoperitoneum required for adequate visualization of intra-abdominal structures is still a concern . With current ongoing research on the efficacy and safety of NOTES it is still premature to advocate it as an alternative to laparoscopic surgery of the biliary tract. Single-incision laparoscopic surgery or SILS refers to the operative technique in which a surgical procedure is carried out through one incision, alternatively it is also known as laparoendoscopic single site (LESS) surgery. In 1997 Navarra et al. described a single-incision laparoscopic cholecystectomy as a plausible alternative procedure to the four-port laparoscopic cholecystectomy . The use of a single umbilical incision to remove the gallbladder was an interesting innovation and, Dacomitinib since Navarra’s initial description, the single-incision laparoscopic cholecystectomy (SILC) procedure has gained momentum.
Many surgical approaches have been defined and implemented in the last few decades. The best Imatinib mechanism method for thoracic disc herniation is still controversial. Except for the laminectomy method that has been abandoned lately, a comparison of the results obtained by studies on various surgical methods indicates that 60 to 80% of the patients recover from the pain or improve their neurological picture. Posterior laminectomy and/or discectomy is the first method used in surgical treatment of thoracic disc herniation . By using this method, it is difficult to decompress midline disc pathologies attached to the dura. The risk of morbidity is high, and even paraplegia may develop. Furthermore, it contains the risk of late kyphotic deformity development [13, 14].
This method has now become historic, and it is not anymore used as a surgical treatment approach for thoracic disc herniation . Transpedicular approach, transfacet pedicle sparing approach, costotransversectomy, and transfacet/transforaminal approach are listed among posterolateral approaches [16�C23]. Perot Jr. and Munro  described the transthoracic approach in 1969 and in 1988 Bohlman and Zdeblick recapitulated this approach. This technique provides access to all levels under T4. It provides direct visibility in central, paracentral, and lateral pathologies . The method proves to be effective in soft and hard pathologies, and it has high efficacy in multilevel pathologies . The method presents high rates of complications such as atelectasis, pleural effusion, and pneumonia, which is a disadvantage.
If the surgeon has to free the diaphragm, hernia may develop. Large arteries or venous structures may be damaged, and left-side approaches bear the risk of infarct and impaired blood supply to the spinal cord due to the obstruction of Adamkiewicz artery. However, Mulier and Debois indicated that even though pulmonary complications may be observed unlike lateral and posterolateral approaches, this approach yielded better neurological improvement . Otani et al. described transthoracic extrapleural approach to reduce the risk of pulmonary complications . The advantages of anterior video-assisted thoracoscopic approach include minimal dissection, low morbidity, no need to retract for rib resection, short hospital stay, and short rehabilitation period.
The biggest disadvantage is that Batimastat the surgeon should be particularly trained to perform this approach. In their study involving 29 patients, Regan et al. reported 76% satisfactory results . Transforaminal endoscopic discectomy is among the methods applicable for thoracic disc disease. It may be used not only for far lateral and foraminal discs but also in midline discs . Transforaminal endoscopic discectomy (TFD) has increased success rates in eligible patients. Computed Tomography helps to discover the bone structure at the preoperative stage.
4,8,9 However, due to undesirable effects after prolonged use, such as pigmentation and taste disturbance, several phytopharmaceutical alternatives to chlorhexidine have been investigated.10,11,12,13,14,15 Higher figure 2 plants and aromatics have traditionally seen widespread use in folk medicine, and many have inhibitory properties against several groups of microorganisms.16,17 Plants from Brazilian biomes have been used extensively as natural medicines by local populations in the treatment of several tropical diseases, including fungal and bacterial infections.16 Lippia sidoides is a typical shrub commonly found in the Northeast Region of Brazil. Its camphoric foliage is indicated as a topical antiseptic agent for conditions of the skin and mucous membranes and also for throat infections.
10,18 The essential oil obtained from L. sidoides is composed mainly of thymol (56.7%�C59.65%) and carvacrol (16.7%�C19%). The other main compounds are caryophyllene (1.1%�C10.6%), p-cymene (7.1%�C9.08%) and myrcene (0.86%�C5.46%).18,19. The composition can vary greatly depending upon the geographic region of collection, variety, and age of the plant, as well as on the methods employed for drying and extraction of the oil.19 Previous studies have indicated that these major components of L. sidoides essential oil exhibit potent antimicrobial activity against oral pathogens18,20 and reduce the severity of gingivitis, dental plaque and histological inflammatory infiltrate in dogs.21 Recently, short-term clinical studies showed a positive effect of L. sidoides-based preparations as preventive agents.
10,22 These initial studies notwithstanding, no published controlled trials have evaluated the efficacy of a L. sidoides-based gel in the control of plaque and gingivitis. Thus, a clinical study in humans was conducted to evaluate the antiplaque and antigingivitis effects of this phytopharmaceutical agent and compare them to those of chlorhexidine. MATERIALS AND METHODS Subjects Thirty adult patients from the University of Fortaleza (15 female and 15 male, age 26�C47 years) were enrolled in this examiner-blinded, parallel, controlled clinical trial. All participants were randomly screened, were informed about the nature of the study, and provided written informed consent for participation, in compliance with the guidelines of the Brazilian National Health Council. The study protocol was approved by the institutional Research Ethics Committee (Co��tica/Unifor report 156/2008) The criteria for inclusion were a bleeding index (BI)23 30%, presence of at least 20 natural teeth, and absence of supragingival calculus and other plaque-retentive Brefeldin_A factors, such as dental caries and restoration excess.
Interestingly, both receptors are less commonly inactivated in MSS colon cancers, which tend to have a worse prognosis than MSI-H colon cancers , and both pathways may be targeted independently. To date, little is known about the distinct selleck chemical Seliciclib contribution of activin signaling to colon cancer development and metastasis and specifically, how TGF�� and activin signaling effects differ despite identical intracellular SMAD signaling. p21 (also known as p21cip1/waf1) is a cyclin-dependent kinase inhibitor controlling cell cycle arrest via cdk1 and 2 inhibition and is a master regulator of multiple tumor suppressor pathways via both p53-dependent and independent mechanisms .
It is a known target gene of TGF�� in colon cancer , and has been associated with activin-induced growth arrest in plasmacytic and breast cancer cells , , but effects of activin on p21 in colon cancer cells as well as downstream consequences have not been assessed. In this study, we explored the mechanisms of TGF�� and activin on p21 regulation and the ensuing functional effects thereof in colon cancers. We found that despite identical intracellular SMAD signaling, TGF�� and activin regulate p21 via diverse mechanisms that are functionally relevant in colon cancer leading to more apoptosis or reduction in growth suppression dependent on the activin/TGF�� signaling status with p21 as a differentially regulated target. Results In the Presence of SMAD4, TGF�� is a more Potent Inducer of Growth Suppression While Activin is a more Potent Inducer of Apoptosis To test and compare the effects of activin and TGF�� on cell growth, we used colon cancer cell lines with differing SMAD4 status as described elsewhere ,  in addition to SMAD4 knockdown.
The ACVR2/TGFBR2/SMAD4 wild type microsatellite stable colon cancer cell line FET and ACVR2/TGFBR2 wild type/SMAD4-null SW480 colon cancer cells were treated with either activin or TGF�� and cellular growth was assessed. As an additional control, SMAD4 was knocked down via siRNA in FET cells which were treated and analyzed accordingly. While both activin and TGF�� treatment led to significant growth suppression in SMAD4 wild type FETs, the effect was more pronounced following TGF�� treatment. In contrast, neither ligand was growth suppressive in the absence of SMAD4 in ACVR2/TGFBR2 wild type/SMAD4-null SW480 colon cancer cells or following SMAD4 knockdown in SMAD4 wild type FET cells (Figure 1A).
Figure 1 In the presence of SMAD4, TGF�� is a more potent inducer of growth suppression and activin a more potent inducer of apoptosis. We then compared apoptosis induction of either ligand in the presence and absence of SMAD4 or p21. Activin induced apoptosis to a greater extent than TGF��, and apoptosis only occurred in the presence of SMAD4 (Figure Brefeldin_A 1B, C).
Analysis of Guaiac-based Fecal Occult Blood Test Occult blood was detected in the feces of 29.4% (5/17) of healthy subjects and 68.2% (15/22) of CRC patients. Thus, the specificity and sensitivity of gFOBT for CRC was 70.6% (95% confidence intervals 44% to 89.7%) and 68.2% (95% confidence intervals merely 45.1% to 86.1%, respectively. A nearly significantly (p=0.09) higher proportion of left-sided CRC (83.3%; 10/12) showed gFOBT positivity compared to right-sided CRC (50%; 5/10) (Table 2, ,33). Analysis of Carcinoembryonic Antigen Serum Level In the case of CEA, two groups were defined: one with elevated CEA serum levels and the other with normal levels. In our study, 14.8% (4/27) of the healthy subjects had elevated CEA levels, while only 51.8% (14/27) of the CRC specimens showed elevated levels.
Thus, the specificity and sensitivity of CEA for CRC was 85.2% (95% confidence intervals 66.3% to 95.8%) and 51.8% (95% confidence intervals 31.9% to 71.3%), respectively. There was no significant difference (p=0.34) between the proportion of left-sided CRC cases (9/15, 60%) and right-sided CRC cases (5/12, 41.6%) with elevated CEA serum levels (Tables 2, ,33). Discussion CRC screening to identify tumors at early stages reduces the mortality of the disease. However, the highly sensitive and specific screening methods (i.e. colonoscopy and CT enterography) are invasive and patient compliance is low. On the other hand, other methods that are not as invasive (i.e., FOBT and CEA) have low specificity and sensitivity. Therefore, a suitable screening method with minimal invasiveness is needed.
In this study, we compared the sensitivity and specificity of methylated Septin 9 as a colorectal biomarker in serum to both gFOBT and CEA serum level. We performed the analysis of gFOBT testing retrospectively for both healthy controls and CRC patients. The 68.2% sensitivity of gFOBT for CRC in our study correlates to previously published results  and the specificity of gFOBT for CRC reached 70.6%. While this method has been used for CRC screening for several decades, it has poor sensitivity due to its non-specificity for gastrointestinal bleeding. It has been shown to reduce both CRC incidence and mortality by 15�C33%. However, testing once is not sufficient, so repeated testing is needed, and in the case of positivity, GSK-3 colonoscopy is recommended. Unfortunately, notable numbers of patients refuse both the repeated gFOBT and the suggested colonoscopy . In our study, occult blood detection from stool was performed only once for each case and gFOBT showed 29.4% (5/17) positivity in the healthy group. However, subsequent colonoscopy did not find any sign of neoplasia or polyps in these cases.
Multivariate analyses were carried out more generally in the framework of additive log-linear Cox and logistic models. Odds ratios fda approved were estimated by using conditional maximum likelihood. Survival functions were estimated by using a Kaplan-Meier estimator (Cox DR, Snell EJ: Analysis of Binary Data. Capman & Hall/CRC, 1989; Klabfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data. John Wiley & Sons, 2002). Statistical analysis was performed by statisticians at the Cancer and Leukemia Group B (CALGB) Statistical Center by using the R statistical environment (version 2.6.1; R Foundation for Statistical Computing, University of Auckland, Auckland, New Zealand; R Development Core Team: A language and environment for statistical computing, 2007. http://www.r-project.org/).
Patients were registered and were randomly assigned to the treatment trial, and clinical data were collected and managed by the Southwest Oncology Group Statistical Center. Tumor samples were received and managed by the CALGB Pathology Coordinating Office. All data were frozen on September 14, 2006. Table A1. Primer and D-HPLC Conditions Used for KIT and PDGFRA Genotyping Studies Exon Forward Primer Reverse Primer D-HPLC Temperatures (��C) K8 GCTGAGGTTTTCCAGCACTC AATTGCAGTCCTTCCCCTCT 50.0 K9 ATGCTCTGCTTCTGTACTGCC CAGAGCCTAAACATCCCCTTA 50.0 K11 CCAGAGTGCTCTAATGACTG ACCCAAAAAGGTGACATGGA 50.0/56.2 K13 CATCAGTTTGCCAGTTGTGC ACACGGCTTTACCTCCAATG 59.5 K17 TGTATTCACAGAGACTTGGC GGATTTACATTATGAAAGTCACAGG 58.0 P12 TCCAGTCACTGTGCTGCTTC GCAAGGGAAAAGGGAGTCTT 50.0/59.7 P14 TGGTAGCTCAGCTGGACTGAT GGGATGGAGAGTGGAGGATT 59.
1 P18 ACCATGGATCAGCCAGTCTT TGAAGGAGGATGAGCCTGAC 50/61.6 View it in a separate window Abbreviation: D-HPLC, denaturing high-performance liquid chromatography. Table A2. Correlation of Imatinib Dose, GIST Genotype, and Objective Response Rate Genotype Imatinib Dose (%) Analysis 400 mg 800 mg OR 95% CI P KIT exon 9 17 67 9.05 1.24 to 116.74 .02 KIT exon 11 71 72 1.05 0.59 to 1.90 .89 WT 42 50 1.39 0.40 to 4.83 .59 View it in a separate window NOTE. Objective response rate includes complete response and partial response rates. Abbreviations: GIST, gastrointestinal stromal tumor; OR, odds ratio; WT, wild type. Table A3. Univariate and Multivariate Analysis of Cofactors Associated With TTP Cofactor Analysis of Progression-Free Survival Univariate Multivariate P HR 95% CI P HR 95% CI KIT mutation Exon 9 .
0022 1.82 1.24 to 2.68 .0008 2.07 1.35 to 3.16 WT .0051 1.53 1.14 to 2.06 .0002 1.85 1.34 to 2.56 Treatment* .69 1.05 0.83 to 1.32 .18 1.18 0.93 to 1.50 Sex, male .06 1.25 0.99 to 1.57 .007 1.41 1.10 to 1.82 Age, by decades .78 0.99 0.90 to 1.08 .74 1.02 0.93 to 1.11 Zubrod performance? 1.6 �� 10?6 2.14 Entinostat 1.57 to 2.92 8.1 �� 10?5 2.02 1.42 to 2.87 ANC .0061 1.07 1.02 to 1.12 .10 1.