Helicobacter pylori (H. pylori) infection with less cost than standard triple therapy. We conducted a randomized, controlled study to compare the efficacies of standard triple therapy and reverse hybrid therapy in the treatment of H. pylori infection.Reverse hybrid therapy is an 1-step 2-phase treatment for H. pylori-infected subjects were randomly allocated to receive either a reverse hybrid therapy  or a standard triple therapy (pantoprazole plus amoxicillin and clarithromycin for 12 days). H. pylori status was assessed 6 weeks after treatment. Additionally, antibiotic resistances and host CYP2C19 genotypes were examined and analyzed.From October 2012 to March 2015, consecutive H. pylori-infected patients were randomly assigned to receive either a reverse hybrid (n = 220) or a standard triple therapy (n = 220). The reverse hybrid group had a higher eradication rate than standard triple group either by intention-to-treat  or per-protocol analysis . The 2 patient groups exhibited similar frequencies of overall adverse events (14.1% vs. 9.5%) and drug compliance (96.8% vs. 98.6%). Clarithromycin resistance was an independent risk factor predicting eradication failure in standard triple group (P < 0.001), but not in reverse hybrid group. CYP2C19 genotypes did not affect the eradication rates in both groups.A total of 440 H. pylori infection since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost.Reverse hybrid therapy can be considered for first-line treatment of  Helicobacter pylori (H. pylori) infection is well recognized as the leading cause of chronic gastritis, peptic ulcer disease, and gastric cancer.5 Currently, H. pylori treatment remains a challenge for physicians as antimicrobial resistance has continued to increase worldwide. Although standard triple therapy has been recommended as the first-line therapy in many guidelines,9 its eradication rate has decreased to unacceptable level in most parts of the world.15 The growing treatment failure rate is generally attributed to an increasing prevalence of resistance to clarithromycin, a basic component of standard triple therapy.15 An updated consensus report8 has therefore proposed a bismuth-containing quadruple therapy or non-bismuth quadruple therapy 18 as first-line treatment in settings with clarithromycin resistance rates greater than 15% to 20%. Although levofloxacin-based triple therapy can achieved a high eradication rate in populations with clarithromycin resistance greater than 20% and quinolone resistance less than 10%,19 it is not generally recommended as a first-line therapy on concerns of the rapid development of resistant strains.20 In its pilot study, hybrid therapy generated excellent eradication rates of 99% and 97% according to per-protocol (PP) and intention-to-treat (ITT) analyses. Subsequent randomized trials demonstrated that hybrid regimens were either comparable with or more effective than sequential therapies.23 Recently, a large multicenter randomized trial also showed that both 14-day hybrid and 14-day concomitant therapies cured more than 90% of the patients with H. pylori infection in areas with high clarithromycin and metronidazole resistance.24 Many experts have recommended hybrid therapy as a treatment option for H. pylori in areas with moderate or high clarithromycin resistance.27Hybrid  therapy developed by Hsu et al. consists of a proton pump inhibitor (PPI) and amoxicillin for 14 days with addition of clarithromycin and metronidazole for the final 7 days.28 Two hundred twenty H. pylori-infected subjects were randomized to receive a 10-, 12-, or 14-day hybrid therapy. The eradication rates with PP analyses were similar: 95.0% for 10-day, 95.1% for 12-day, and 93.4% for 14-day hybrid therapies.28 The results suggested that the duration of hybrid therapy could be reduced to 12 days or less while maintaining the high eradication rate.Recently, we further tested whether the duration of hybrid therapy could be reduced while maintaining the high eradication rate.H. pylori infection.29From the perspective of clinical practice, reversing the drug administration sequence in hybrid therapy  simplifies the treatment and makes it an 1-step 2-phase therapy , ingestion of antibiotics or bismuth within the prior 4 weeks, and pregnancy.All consecutive Using a computer-generated number sequence, we randomly allocated patients at a 1:1 ratio to either a 12-day reverse hybrid therapy  or a 12-day standard triple therapy (pantoprazole 40 mg plus clarithromycin 500 mg and amoxicillin 1 g twice daily for 12 days). All drugs were taken 1 hour before breakfast and dinner. An independent research assistant at the Kaohsiung Veterans General Hospital generated the computerized random number sequence. She prepared the study medicines and instructions for drug administration according to the number sequence and concealed them in an opaque envelope. The opaque envelopes labeled with sequence numbers outside were kept by research nurses at each study hospital.After written informed consent was obtained from each participant, the independent research assistant at the Kaohsiung Veterans General Hospital reported by telephone each patient's treatment allocation to the research nurses at each study hospital. The patients took medicines according to the instructions in the envelopes. Both physicians and research nurses were blind to the treatment arm.H. pylori eradication.Patients were followed in outpatient clinics to investigate adverse effects and drug compliance at the second week. An additional 4-week pantoprazole (40 mg once daily) therapy was administered following eradication treatment for the patients with peptic ulcer disease. In contrast, the patients with gastritis only received 4-week antacid therapy following CYP2C19 genotypes, blood sampling was performed on enrollment. DNA was extracted from the leucocytes with a commercially available kit . Genotyping procedures for identifying the CYP2C19 wild-type gene and 2 mutated alleles, CYP2C19 m1 and CYP2C19 m2, were performed by polymerase chain reaction-based restriction fragment length polymorphism as previous description.30 Genotypes were classified into 3 distinct groups: homogeneous extensive metabolizer (homEM); heterogeneous extensive metabolizer (hetEM); poor metabolizer (PM).Participants completed a standard questionnaire which contained questions regarding demographic data and personal history of smoking and alcohol consumption. For the analysis of 31 Compliance with therapy was determined via pill counts.Adverse events were assessed by a specific questionnaire fulfilled at the end of eradication therapy. The severity of adverse events were recorded according to a 4-point  scale system as previous description.H. pylori status. Cure of H. pylori infection was defined as a negative result of urea breath test, or negative results of all histology, urease test, and bacterial culture.32Patients with gastric ulcer on enrollment received a follow-up endoscopy with rapid urease test, histological examination and culture 6 weeks after the end of eradication therapy. In contrast, patients with gastritis or duodenal ulcer underwent a urea breath test to assess final H. pylori culture was only conducted in the Kaohsiung Veterans General Hospital. We took a specimen from the antrum for culture of H. pylori.33 and then rubbed the specimen on the surface of an agar plate . The agar plate was incubated at 37°C with microaerobic condition for 5 days. If one or more colonies of Gram-negative bacilli were positive in urease, catalase, and oxidase tests, the culture result was considered positive. The E-test  was used to evaluate the resistance to antibiotics according to minimum inhibitory concentration (MIC) values of >1, >0.5, and >8 μg/mL for clarithromycin, amoxicillin, and metronidazole, respectively.34Because of facility problems, H. pylori infection. PP analysis only included patients with good drug compliance and excluded patients with unknown H. pylori status following therapy. The second outcomes were the frequency of adverse events and drug compliance. Compliance was defined as good (taking at least 80% of eradication medication) or poor . Differences in demographic data, eradication rates, and adverse events among different arms were determined by Chi-square test or Fisher exact test, as appropriate. The Student t test was used for the comparison of continuous data. SPSS (version 12.0 for Microsoft Windows) were used for all statistical analyses. A P-value of <0.05 was considered statistically significant.Eradication rate was the primary outcome of this study. It was evaluated by ITT, modified ITT and PP analyses. ITT analysis included all eligible patients enrolled in the study regardless of compliance with the study protocol. Patients with unavailable data following treatment were assumed to have been treated unsuccessfully. Modified ITT analysis included all those receiving at least 1 dose of drug and undergoing follow-up tests for 35 the eradication rate of 12-day standard triple therapy was 85%. It was estimated that at least 220 participants in each group were required to achieve a statistic power of 90% with a type I error of 0.05, assuming a 15% loss to follow-up and 4% of participant with poor medication compliance.According to previous studies,To identify the independent factors determining the eradication rate, clinical, genetic, and bacterial parameters were initially analyzed by univariate analysis. The parameters with significant differences in univariate analysis were then further analyzed by a logistic regression method to search the factors independently predicting eradication rate.H. pylori-infected patients were recruited for the study and randomly allocated to the reverse hybrid (n = 220) or standard triple group (n = 220). The baseline demographic and clinical characteristics of patients in both groups are shown in Table From October 2012 to March 2015, a total of 440 P = 0.016). The modified ITT (95.4% vs. 88.4%) and PP analyses (95.7% vs. 88.3%) yielded similar results .The outcomes of treatments are listed in Table H. pylori culture was performed in 230 patients at initial endoscopy. H. pylori strains were isolated from 184 (80.6%) of them. Antibiotic resistance rates in each group are listed in Table H. pylori strains isolated in this trial were 10.3% (19/184), 0.0% (0/184) and 24.5% (45/184), respectively. Reverse hybrid therapy achieved a higher eradication rate for clarithromycin-resistant strains than standard triple therapy . However, the 2 therapies had comparable eradication efficacy for clarithromycin-sensitive strains (99% vs. 97%). There were no differences in treatment efficacy between the 2 therapies for either metronidazole-sensitive (100% vs. 93%) or resistant strains (91% vs. 81%). In the reverse hybrid therapy group, the eradication rates of the strains with nonresistance, single clarithromycin resistance, single metronidazole resistance, and dual resistances were 100%, 100%, 95%, and 67%, respectively. The corresponding eradication rates in the standard therapy were 99%, 33%, 90%, and 0%, respectively. Reverse hybrid therapy had a higher eradication rate for single clarithromycin-resistant strains than standard triple therapy (P = 0.021).P = 0.14).The incidences of adverse events in the participants receiving reverse hybrid and standard triple therapies were 14.1%  and 9.5% , respectively. The 2 therapies exhibited similar frequencies of overall adverse events (P = 0.03). There were no significant differences in the frequencies of other adverse events between groups. Three patients in the hybrid group stopped the anti-H. pylori medication because of abdominal pain (n = 1), headache (n = 1), and dizziness (n = 1). In the standard triple group, 3 patients discontinued treatment owing to diarrhea (n = 1), dizziness (n = 1), and skin rash (n = 1). Reverse hybrid and standard triple groups displayed similar compliance rates .Table P = 0.033), presence of peptic ulcer (P = 0.002), and clarithromycin resistance (P < 0.001), but not by host CYP2C19 genotype and other clinical factors (Table P < 0.001).Univariate analysis for the clinical, host, and bacterial factors did not identify any risk factors associated with treatment failure by reverse hybrid therapy Table . The erars Table . MultiplH. pylori infection should be highly effective, well tolerated, simple, and inexpensive. This study is the first to conduct a head-to-head, randomized, controlled trial to assess the efficacy of 12-day standard triple therapy and that of 12-day reverse hybrid therapy for H. pylori eradication. The results clearly showed that 12-day reverse hybrid therapy achieved a higher eradication rate than 12-day triple therapy, whether by ITT (93.6% vs. 86.8%), modified ITT (95.4% vs. 88.4%), or PP analyses (95.7% vs. 88.3%). The 2 treatments were well tolerated and shared comparable total adverse events (14.1% and 9.5%) and compliance (96.8% and 98.6%). With regard to pharmaceutical cost, 12-day reverse hybrid therapy was cheaper than 12-day triple therapy (0.37.2 vs. 0.44.0 in Taiwan). The data support the use of reverse hybrid therapy as the standard first-line treatment for H. pylori infection.With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has recently declined to less than 80% in many countries. An ideal treatment for H. pylori therapy.35 Numerous previous reports13 disclosed that clarithromycin resistance is the key factor determining the treatment efficacy of standard tripe therapy. According to the theoretical effect of increasing clarithromycin resistance on the success of standard triple therapy, PP eradication rate falls to 90% with 5% clarithromycin resistance for 7-day therapy and 15% resistance for 14-day therapy.36 Two recent randomized controlled trials confirmed that the 7-day standard triple therapy had a cure rate of 82% in an area with 18% clarithromycin resistance,18 and 14-day standard triple therapy achieved an eradication rate of 87% in an area with 11% clarthromycin resistance.37 In the present study, the clarithromycin resistant rate of H. pylori strains in the study population was 10.3%. The 12-day standard triple therapy failed to surpass a 90% eradication rate . In contrast, 12-day reverse hybrid therapy achieved an eradication rate ≥95% . Molina-Infante and his colleagues24 also confirmed that 14-day hybrid therapy cured more than 90% of H. pylori infections in areas with high clarithromycin (24%) and metronidazole resistance (34%). The aforementioned data strongly indicate that reverse hybrid therapy can replace the standard triple therapy as the first-line treatment for H. pylori infection in areas with clarithromycin resistance ≥10% since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost.As a general rule for the treatment of other infectious diseases, clinicians should prescribe therapeutic regimens that have a PP eradication rate ≥90% for anti-H. pylori eradication therapy are acid-sensitive. PPIs can increase the activity of some antibiotics by reducing gastric acid secretion and possess direct anti-H. pylori activity.38 Most of them are metabolized by the hepatic cytochrome P450 system, especially CYP2C19.38 Several previous reports demonstrated that the CYP2C19 homEM genotype was an independent factor determining the success rate of H. pylori eradication therapy.39 In this study, the subjects with CYP2C19 homEM genotype had a lower eradication rate than those with PM genotype (100% vs. 94%) in the reverse hybrid therapy group. However, the difference did not reach statistical significance. In the stand triple therapy group, there were also no significant differences in eradication rates among the subjects with homEM, hetEM, and PM genotypes.Many antibiotics applied in 28 were comparable . The data suggest that both reverse and standard hybrid regimens can achieve an eradication rate exceeding 90% in the first-line treatment of H. pylori infection.To simplify eradication regimen, the sequence of drug administration in hybrid therapy was reversed in this study Fig. . PatientH. pylori strains with antibiotic susceptibility data in either reverse hybrid or standard triple therapy group was too small to make a robust conclusion for the impacts of antibiotic resistances on the eradication rates of each therapy. Second, the study was conducted in a single country. The results are therefore needed to be confirmed in other countries with different patterns of antibiotic resistances. However, this study is the first trial comparing reverse hybrid therapy and standard triple therapy in the treatment of H. pylori infection. Additionally, it is a randomized-controlled trial with large sample size (>400 participants).Our study had several limitations. First, the number of H. pylori infection in areas with clarithromycin resistance ≥10% since the new one-step therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost.In conclusion, reverse hybrid therapy can replace the standard triple therapy as the first-line treatment for


Half of gastric MEN responded to intraganglionic volume injection as well as to ganglionic stretch and 23% responded to stretch only. Tension-sensitive MEN were to a large proportion USAMEN (44%). In summary, we demonstrated for the first time compression and tension-sensitive MEN in the stomach; many of them responded to one stimulus modality only. Their proportions and the basic properties were similar to MEN previously identified by us in other intestinal region and species. Unlike in the intestine, the responsiveness of some gastric MEN is enhanced by extrinsic TRPV1 expressing visceral afferents.For long it was believed that a particular population of enteric neurons, referred to as intrinsic primary afferent neuron (IPAN)s, encodes mechanical stimulation. We recently proposed a new concept suggesting that there are in addition mechanosensitive enteric neurons (MEN) that are multifunctional. Based on firing pattern MEN behaved as rapidly, slowly, or ultra-slowly adapting RAMEN, SAMEN, or USAMEN, respectively. We aimed to validate this concept in the myenteric plexus of the gastric corpus, a region where IPANs were not identified and existence of enteric sensory neurons was even questioned. The gastric corpus is characterized by a particularly dense extrinsic sensory innervation. Neuronal activity was recorded with voltage sensitive dye imaging after deformation of ganglia by compression (intraganglionic volume injection or von Fry hair) or tension (ganglionic stretch). We demonstrated that 27% of the gastric neurons were MEN and responded to intraganglionic volume injection. Of these 73% were RAMEN, 25% SAMEN, and 2% USAMEN with a firing frequency of 1.7 (1.1/2.2), 5.1 (2.2/7.7), and of 5.4 (5.0/15.5) Hz, respectively. The responses were reproducible and stronger with increased stimulus strength. Even after adaptation another deformation evoked spike discharge again suggesting a resetting mode of the mechanoreceptors. All MEN received fast synaptic input. Fifty five percent of all MEN were cholinergic and 45% nitrergic. Responses in some MEN significantly decreased after perfusion of TTX, low Ca The enteric nervous system (ENS) forms along the gastrointestinal tract a continuous network of ganglia interconnected via nerve bundles. These ganglia are made up of neurons that are able to regulate all gastrointestinal functions autonomously from the central nervous system. To function in an autonomous way, such a system requires neurons specialized to sense different stimuli. For many years prevailed the plausible concept proposing the existence of specialized neuronal populations, functionally defined as sensory, inter and motor-neurons. Such neuron populations had distinct morphologies, chemical codes and projections which mostly fitted to their functions. In the last few years we and others identified mechanosensitive enteric neurons that did not fulfill these strict criteria but had features that rather classified them as multifunctional neurons  in the guinea pig ileum s with the electrophysiological feature of a slow after hyperpolarization (AH) are absent in the myenteric plexus of the guinea pig gastric corpus  and approved by the Bavarian state ethics committee  according to §4 and §11 Deutsches Tierschutzgesetz under the reference number 32-568-2.2, 5% CO2; pH = 7.40) Krebs solution containing (in mM): 117 NaCl, 4.7 KCl, 1.2 MgCl2 6 H2O, 1.2 NaH2 PO4, 25 NaHCO3, 2.5 CaCl2, 2 H2O, 11 glucose. The mucosa, the submucosa and the circular muscle layer of the corpus were gently removed in order to obtain a longitudinal muscle-myenteric plexus preparation. This preparation (5 × 10 mm) was pinned onto a silicone ring that was placed in a recording chamber continuously perfused with 37°C carbogen bubbled Krebs solution with a rate of perfusion of 11 ml/min. After mounting the tissue the average amount of stretch above slack was 29% ± 3% in the circular and 48% ± 9% in the longitudinal direction.Male guinea pigs “Dunkin Hartley”  were used. Guinea pigs (340 ± 60 g) were killed by cervical dislocation followed by exsanguination. The stomach was quickly removed and further dissected in Carbogen aerated  98 NaCl, 4.7 KCl, 16 MgCl2 6 H2O, 1.2 NaH2 PO4, 25 NaHCO3, 0.25 CaCl2 H2O, 11 glucose, was used.To block synaptic transmission 20 min perfusion of the entire tissue with a low Ca2/pixel. The fluorescent images were acquired and processed by the Neuroplex 9.9.6 software (RedShirt Imaging).An ultra-fast neuroimaging technique coupled with a voltage sensitive dye was used. Individual ganglia were loaded with the fluorescent voltage-sensitive dye Di-8-ANEPPS (1-(3-sulfanatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphthyl]vinyl] pyridinium betaine)  by local application through a microejection pipette loaded with 20 μM Di-8-ANEPPS dissolved in DMSO and pluronic F-127 containing Krebs solution. This staining did not change the electrophysiological properties of the nerve cells  connected to a constant-voltage stimulator was used (600 μs pulse duration with amplitudes ranging from 1 to 8 V which were supra-threshold).The mechanical stimulation techniques used are the intraganglionic injections of small volumes of Krebs solution, von Frey hair probing  and ganglionic stretch  for 400 ms. The pressure was adjusted to values that led to deformation of the entire ganglion as visually inspected. As previously described, the intraganglionic volume injection caused a biphasic deformation  which was connected to a motorized micromanipulator  to control its advancement. The hair was placed 1–2 μm above the ganglion and then advanced to create ganglion deformation with a step size of 10 μm, then left in place for 1 min and finally retracted.Ganglionic stretch was achieved by forcing apart two L-shaped wires which were positioned onto the tissue ~100 μm above and below a ganglion. One of the wires was connected to a motorized micromanipulator ; the other wire was just placed onto the tissue. The mobile wire was moved at a speed of 150 μm/s perpendicular to the ganglion axis. This type of stimulus also caused an initial fast dynamic deformation lasting for 1234 ± 525 ms followed by a sustained deformation when the wire stayed in place to maintain tissue stretch.This allowed us to study responses to different kinds of mechanical stresses. While stretch caused elongation and thereby a tensile stress, intraganglionic injection evoked a mixture of compressive and shearing forces.Preliminary experiments to ensure reproducibility of the responses were performed repeating the stimulations at least three times at 5–10 min intervals. Moreover, after fixation of the tissue, any possible cell damage could be excluded by immunohistochemical staining for Hu C/D neuronal protein antibody that allowed us to check for intact cellular morphology.+ channels. As previously reported we blocked glia response evoked by mechanical stimulation by 2 μM of the phospholipase C blocker U73122  was used to block the voltage-gated NaBefore adding the substances two control mechanical stimulations were performed. Then, the antagonists were added to the perfusing Krebs solution for 25 min and another mechanical stimulation was performed. When the substance had a reversible effect, another mechanical stimulus was applied after 30 min wash out.Tissue specimens were fixed overnight at room temperature in a solution containing 4% paraformaldehyde and 0.2% picric acid in 0.1 mol/l phosphate buffer and then washed (3 × 10 min) in phosphate buffer. The preparations were first incubated in phosphate buffered saline (PBS)/NaN3 (0.1%)/horse serum  for 1 h at room temperature followed by 48 h and 12 h incubation with the primary and secondary antibody, respectively. As primary antibodies we used Hu C/D neuronal protein antibody biotin conjugated , goat anti choline acetyltransferase , rabbit anti nitric oxide synthase , rabbit anti-Calb  and rabbit anti transient receptor potential vanilloid (TRPV)1 . As secondary antibodies we used donkey anti-rabbit conjugated to 7-amino-4-indodicarbocyanin , streptavidin conjugated to dichlorotriazinylaminofluorescein , donkey anti goat Cy5 , and donkey anti rabbit conjugated to CF 488 .3 (0.1) containing 65% glycerol. The preparations were examined with an epifluorescence microscope (Olympus), equipped with appropriate filter blocks. Images were acquired with a video camera  connected to a computer and controlled by the “Analysis” software (Olympus). Frame integration and contrast enhancement were employed for image processing. Besides specifications provided by the suppliers, specificity of primary antibodies were previously published for rabbit anti NOS /NaNWe counted the number of labeled neurons in each ganglion and we analyzed the number of mechanosensitive neurons per ganglion and the frequency of their action potentials discharge. In addition the duration of spike discharge was calculated. We additionally analyzed an adaptation index (AI) of the mechanosensitive neurons with the following equation , Igor Pro 6.22A  and Image J 1.43u  software. For movie editing the program Lightworks  was used. The statistical analyses and graphics were performed with Sigmaplot 12.5 . Data are presented as mean ± standard deviation or, when not normally distributed, as median values together with the 25 and 75% quartiles given in brackets. Differences in the spike frequency between several control stimulations were performed with a One-way repeated measures analysis of variance (ANOVA) test. Action potential frequency in the same neuron and number of responding neurons in the same ganglion after 2 subsequent stimuli were tested with a paired Intraganglionic volume injection was performed in 40 ganglia from 23 guinea pigs. Of all neurons in a given ganglion, 27 ± 15% were mechanosensitive. The dynamic deformation lasted for 469 ± 179 ms. The flow rate was 502 ± 69 μm/s. The degree of ganglion deformation expressed as percentage change in the ganglionic area after intraganglionic volume injection was with 0.2 (0.0/0.7)% almost negligible. In the myenteric plexus of the gastric corpus 73% of the mechanosensitive neurons were identified as RAMEN, 25% as SAMEN, and 2% as USAMEN : I stimulation 1.4 (0.1/2.6) Hz, II stimulation 1.4 (0.7/4.3) Hz, III stimulation 2.0 (0.7/3.8) Hz, and IV stimulation 2.0 (0.7/5.1) Hz . It has to be noted that this meant additional deformation with each injection as there was not sufficient time for volume redistribution to regain the original ganglion shape. Despite this, the firing pattern remain similar and frequency was not significantly different between the four stimulations . These pressures were set at the gauge and we cannot comment on the actual intraganglionic pressure changes. The percentage of mechanosensitive neurons gradually increased from 0 (0.0/10.1)%, 10.7 (3.0/21.4)% to 19.4 (12.7/33.3)%. The spike discharge also increased with increasing pressure (28 neurons): 0.6 (0.0/3.2), 3.6 (1.7/5.5), and 5.2 (2.3/7.6) Hz. The enhanced spike frequency was associated with a slower adaptation reflected by the change in RAMEN:SAMEN:USAMEN proportion: with 40 Kpa 87.5% of the neurons were RAMEN and 12.5% SAMEN, with 60 Kpa 78% RAMEN and 22% SAMEN and with 100 Kpa 60% RAMEN, 36% SAMEN and 4% USAMEN.++/high Mg++ Krebs solution. After all fast EPSPs were blocked we performed another mechanical stimulation and found that the proportion of mechanosensitive neurons was significantly reduced from a median of 22 (12/29)% to 14 (7/27)% per ganglion (p = 0.016). The overall firing frequency of those 48 neurons which still responded in the presence of low Ca++/high Mg++ Krebs solution was not significantly different: 1.7 (1.0/3.0) Hz vs. 1.3 (0.5/2.8) Hz. Before and after synaptic blockade the proportion of RAMEN, SAMEN, and USAMEN remained with 75, 17, and 8% the same.In 12 ganglia from six guinea pigs we perfused the entire tissue with low Cap = 0.02; five ganglia, four guinea pigs). The overall spike frequency of the 15 neurons that still fired in TTX was also significantly lowered by the toxin from 1.7 (1.1/2.8) to 1.1 (0.6/1.1) Hz. The neurons still responding in TTX were 88% RAMEN, 6% SAMEN, and 6% USAMEN.We previously showed that action potentials of myenteric neurons in the gastric corpus evoked by intracellular current injection were exclusively carried by TTX-sensitive sodium influx  ΔF/F. After perfusion with low CaIntraganglionic volume injection is not widely used as a mechanical stimulus. We therefore performed parallel experiments using intraganglionic volume injection and the well-established von Frey hair probing Figure . While tp = 0.002). We identify 27 ± 14 neurons per ganglion responding to ganglionic stretch. From these neurons 12% were defined as RAMEN, 44% as SAMEN, and 44% as USAMEN . The overall firing frequency of 48 neurons was significantly decreased from 2.1 (1.0/4.1) to 0.5 (0.0/2.2) Hz (p < 0.001). The firing behavior did not change after capsaicin application as 61% of the neurons were RAMEN, 30% SAMEN, and 9% USAMEN.As described above, responses in some MEN depend on synaptic release, a phenomenon which we have not observed in intestinal MEN in guinea pig or mouse . After TRPV1 blockade the proportion of RAMEN, SAMEN and USAMEN remained with 73, 23, and 4%, respectively, unchanged.In 12 ganglia from four guinea pigs, we perfused the tissue with the TRPV1 antagonist capsazepine. We observed a significant reduction in the number of MEN from 35 (20/51) to 28 (14/44)%. The overall spike frequency from 100 MEN was decreased from 1.7 (1.1/3.8) to 1.1 (0.1/3.3) Hz  from 1.9 (1.1/5.2) to 1.1 (0.0/2.6) Hz (p = 0.003). The firing pattern of the mechanosensitive neurons after SR142801 perfusion revealed 61% RAMEN, 39% SAMEN, and no USAMEN.Extrinsic TRPV1 expressing afferents release SP. In four ganglia from four guinea pigs we therefore tested whether the NK3 antagonist SR142801 would mimic the effects of capsaicin and capsazepine. Although the number of MEN remained constant (27 (22/36) vs. 22 (12/27)%) we found a significant decrease in overall spike frequency (In the gastric myenteric plexus 67% of myenteric neurons were ChAT-immunoreactive (IR) while 29% were NOS-IR , suggesting a similar pool of neurons in each gut region responsible for detecting and reacting to compressive forces. In both regions, RAMEN prevailed but the distribution of RAMEN, SAMEN, and USAMEN was nevertheless different between the two regions .Compression by intraganglionic volume injection identified 27% of all neurons as mechanosensitive. This proportion was not different from the guinea pig ileum (Mazzuoli and Schemann, Mechanosensitive responses in RAMEN were reproducible after back-to-back intraganglionic injection which every time imposed a compressive force on top of a sustained deformation. These data led us to conclude that these mechanoreceptors did not desensitize but rapidly reset. This property is best known for cardiovascular mechanoreceptors (Xavier-Neto et al., We found 27% tension sensitive neurons with about 50% also responding to compression by intraganglionic volume injection. The change in ganglionic area was about ~3% which is much smaller than the 95% increase in ganglionic area described in a distended ileal segment (Gabella and Trigg, All MEN received fast EPSPs indicating that their activity may be synaptically modulated. This was not unusual and in this respect MEN resembled primary afferents neurons of the mesencephalic ganglion of the trigeminal nerve receiving synaptic inputs have been described (Verdier et al., ++ was indeed described in enteric glia after mechanical stimulation (Zhang et al., We have shown previously that primary cultured MEN and MEN in freshly dissected preparations responded directly to the mechanical deformation (Kugler et al., A small proportion of MEN still responded when TTX was perfused. This was due to blockade of somal spikes because action potentials in myenteric neurons of the gastric corpus evoked by intracellular current injection were abolished by TTX (Schemann and Wood, Blockade of synaptic transmission, as well as defunctionalization of extrinsic afferents by long term capsaicin application resulted in a decreased number of neurons responding to deformation. This is different from the results in MEN of guinea pig ileal myenteric plexus where neither synaptic blockade nor capsaicin application affected responsiveness of mechanosensitive neurons (Mazzuoli and Schemann, Calbindin was found to be a quite reliable marker of AH-IPANs in the guinea pig ileum. It was not a good marker for MEN in the gastric corpus, as only 1% of the mechanosensitive neurons were positive for this calcium binding protein. This agrees with our previous results in the guinea pig ileum where calbindin was expressed by only a small proportion of MEN (Mazzuoli and Schemann, In summary we identified in the guinea pig gastric corpus a population of cholinergic and nitrergic MEN which responded to compressive and/or tensile forces. While compression evoked rapid adaptation of firing, spike discharge after stretch was more sustained and adapted slowly or even ultra-slowly. Compared with the small intestine, a major difference with gastric MEN was that extrinsic afferents appeared to contribute to their mechanosensitivity. With this study we can also conclude that multifunctional MEN with comparable properties are present throughout the gut.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A panorama of mucocutaneous manifestations is produced by HIV infection which correlates with the degree of immunodeficiency. Viral, bacterial and fungal infections, as well as inflammatory skin diseases, have all been reported to increase as CD4 T cells are depleted. Since the introduction of HAART, there has been a dramatic decrease in the incidence of HIV associated dermatoses. However, initiation of ART itself causes various cutaneous adverse effects. Our goal was to study the various mucocutaneous manifestations encountered in treatment naïve HIV infected and those on ART.This study involved a cross sectional assessment of 85 HIV seropositive patients attending STD and ART clinic. Of which 16 patients were not on HAART and the rest 69 were on HAART.p<0.0001). Six months post HAART, the mean CD4 count had significantly increased to 515.44± 245.54 (p <0.001). The incidence of mucocutaneous manifestations were similar in both the groups (p=0.4891). The most common infections in those not on HAART were fungal (25%), viral (12.5%), bacterial (6%). And among those on HAART were fungal (43%), viral(25.5%) and bacterial(2.8%). The various adverse cutaneous reactions to HAART observed in our study were lipodystrophy (14%), maculopapular rash(7.2%) lichenoid eruptions(5.2%).The mean baseline CD4 count of those not on HAART was 571.94±278.44 and mean baseline CD4 count of those on HAART was 281.88± 231.02 and the difference was significant (These findings indicate that HAART often reduces the incidence of infectious skin diseases in patients with HIV, but can itself be the cause of drug eruptions.


Trypanosoma brucei gambiense causes Gambian trypanosomosis, a disease ravaging affected rural parts of Sub-Saharan Africa. We screened 1200 human blood samples for T. b. gambiense using the card agglutination test for trypanosomosis, characterized trypanosome isolates with Trypanosoma gambiense serum glycoprotein-PCR (TgsGP-PCR), and analyzed our data using Chi square and odds ratio at 95% confidence interval for statistical association. Of the 1200 samples, the CATT revealed an overall infection rate of 1.8% which ranged between 0.0% and 3.5% across study sites. Age and sex based infection rates ranged between 1.2% and 2.3%. We isolated 7 (33.3%) trypanosomes from the 21 seropositive samples using immunosuppressed mice which were identified as T. b. gambiense group 1 by TgsGP-PCR. Based on study sites, PCR revealed an overall infection rate of 0.6% which ranged between 0.0% and 1.5%. Females and males revealed PCR based infection rates of 0.3% and 0.8%, respectively. Infection rates in adults (1.3%) and children (0.1%) varied significantly (p < 0.05). We observed silent T. b. gambiense infections among residents of this focus. Risks of disease development into the second fatal stage in these patients who may also serve as reservoirs of infection in the focus exist. Trypanosoma brucei gambiense causes the Gambian sleeping sickness, a very chronic, debilitating, complex, and fatal parasitic zoonosis ravaging affected rural parts of Sub-Saharan Africa. The disease transmitted by tsetse flies is widespread in the Sub-Saharan African region posing serious public health problems in the region and to tourists visiting tropical Africa [l Africa , 2. It i Glossina palpalis, G. tachinoides, and G. fuscipes. These vectors are especially common at watering places like rivers or lakes where people frequently visit to collect water and do their washing and animals visit to drink water [In natural conditions, transmission of the parasite is cyclical through bites of infected tsetse flies includingnk water . The parnk water , 5.The pathogen is ranked 9th of the 25 human infectious diseases in Africa based on its socioeconomic impact  and is i T. b. gambiense in the Gboko sleeping sickness focus was first reported in 1974, and since then no successful attempt has been made to control the disease in the affected region [ T. b. gambiense in humans in the old Gboko sleeping sickness focus in Nigeria and characterized isolates using TgsGP-polymerase chain reaction.In Nigeria however, human infection withThis study was carried out around the old Gboko sleeping sickness focus which is located in the northern part of Nigeria between longitudes 7°47′ and 10°00′ east and latitudes 60°25′ and 8°8′ north. It shares boundaries with five other states, namely, Nasarawa (north), Taraba (east), Cross River (south), Enugu (southwest), and Kogi (west), and with the Republic of Cameroon to the southeast . The majWe conducted a cross-sectional study around the old Gboko sleeping sickness focus in Nigeria within six Local Government Areas (LGAs), namely, Gashaka, Gboko, Ibi, Karim Lamido, Ukum, and Vandeikya, considering their relationships with the Gboko and Fontem sleeping sickness foci and the Gashaka-Gumti and Yankari game reserves. Human subjects were sampled systematically from each household by selecting every 5th household following the order in which houses were built, and individuals were selected using balloting by names. T. b. gambiense as described by Magnus et al. [Two millilitres of blood was aseptically collected from each human subject via the median cubital vein using a 5 mL syringe and 21 G needle and transferred immediately into clean labelled sample bottles containing ethylene diamine tetra-acetic acid (EDTA) at 1.5 mg/mL of blood  and gents et al. . All CAT T. b. gambiense specific LiTat 1.3 antibodies using a purified T. b. gambiense variable surface antigen.The CATT test kits were obtained from the Institute for Tropical Medicine, Antwerp, Belgium. Blood samples were analyzed using the CATT as described by Magnus et al. . This teMice were obtained from the Small Animal Experimental Unit of the National Veterinary Research Institute, Vom, Nigeria, for the study. The mice were appropriately labelled and screened for ectoparasites and endoparasites by standard techniques  and acclThe bloodstream form trypanosomes isolated from humans and propagated in mice were separated from the infected mice blood using a DEAE 52 column  as described by Lanham and Godfrey . These pTrypanosome DNA extraction was done using GeneJET genomic DNA extraction kit  using the method described by Oury et al. . The ext Trypanosoma isolates. Cycling conditions for TgsGP-PCR were denaturation at 98°C for 10 seconds to activate the Phusion Flash II DNA Polymerase, followed by 40 cycles with denaturation at 98°C for 1 second, annealing at 63°C for 30 seconds, 30-second elongation at 72°C, and a final extension at 72°C for 5 minutes as recommended by the manufacturer. All amplified products were analyzed by electrophoresis in a 2% agarose gel and UV illumination after ethidium bromide staining.The TgsGP primer set with sequences forward 5′-GCTGCTGTGTTCGGAGAGC-3′ and reverse 5′-GCCATCGTGCTTGCCGCTC-3′  was used T. b. gambiense were calculated by dividing the number of infected individuals by the total number of individuals examined and expressed as percentages. This was done for different variables such as study sites, sex, and age. The Chi square (χ2) test and odds ratio were used where appropriate to compare the prevalence rates based on different variables and values of p < 0.05 were considered significant.All data obtained during the study were analyzed using GraphPad Prism 4.0. Infection rates of Trypanosoma brucei gambiense as shown in A total of 1200 human blood samples from 6 sites around the old Gboko sleeping sickness focus were analyzed using the CATT and PCR for the presence ofThe CATT revealed an overall infection rate of 1.8% of the 1200 samples studied. Based on the 6 sites studied, Gashaka, Gboko, Ibi, Karim Lamido, Ukum, and Vandeikya recorded infection rates of 3.5% (7/200), 2.5% (5/200), 0.5% (1/200), 2.5% (5/200), 0.0% (0/200), and 1.5% (3/200), respectively . Sex bas Trypanosoma gambiense serum glycoprotein- (TgsGP-) PCR as group 1 of T. b. gambiense. PCR revealed an overall infection rate of 0.6% of the 1200 samples analyzed. PCR based infection rates in relation to study sites were 1.5% (3/200) and 1.0% (2/200) for Gashaka and Gboko, respectively (p < 0.05) between the 1.3% (6/450) and 0.1% (1/750) infection rates recorded by adults and males, respectively.Trypanosomes were isolated from 7 (33.3%) of the 21 seropositive samples using immunosuppressed mice. These isolates were characterized using theectively . Both Kaectively . Females T. b. gambiense considering the low parasitaemia associated with this parasite. Mice were inoculated with cyclophosphamide at 200 mg per kg body weight to suppress mice immunity due to the low parasite isolation rate reported for this parasite [In our study, we inoculated human seropositive samples into mice to propagateparasite . Isolate T. b. gambiense infections in this old sleeping sickness focus. Previous report showed that Gboko was endemic for the pathogen [ T. b. gambiense, and the increasing trend of treatment failure [We observed silentpathogen . The finpathogen  and therpathogen  might hapathogen , the hig failure  might ha T. b. gambiense. The extension of the Yankari game reserve forest into the Jevjev and Binari areas of Karim Lamido may explain also the high prevalence observed in the area. The riverine nature of this region might have contributed to the high prevalence observed as riverine areas are known to promote tsetse breeding.The overall seroprevalence rate of 1.8% revealed by this study is lower than the earlier report by Karshima et al.  in a reg T. b. gambiense in relation to sex are in agreement with the earlier report by Karshima et al. [The variations in the prevalence ofa et al. , who alsa et al.  who repo T. b. gambiense and is shown to confer resistance to human serum. We were able to isolate and characterize 7 stocks from 21 CATT seropositive humans. The high specificity of the PCR technique may be a reason for the low infection rate revealed by the technique. On the other hand it was also possible that the CATT detected inactive infections where antibodies have not completely disappeared from the blood.One of the major objectives of this study was to isolate and characterize trypanosome isolates from serologically positive humans. This objective was achieved by the detection of the TgsGP gene which is present in only one strain of the 3 trypanosomes pathogenic to man. This gene is specific to group 1 T. b. rhodesiense and types 1 and 2 T. b. gambiense which respond differently to HAT chemotherapy [ T. b. gambiense among all human isolates since it has been reported to be associated with over 90% of cases of human African trypanosomosis [The epidemiological and clinical significance of detecting only one species of human infective trypanosomes in the study area is that the risk of treatment failure associated with mixed infections ofotherapy  will be osomosis , 5. T. b. gambiense infections among residents of this old sleeping sickness focus. Infections were more prevalent in children and males. The epidemiological implication of this finding is the risk of tsetse flies spreading these silent infections to uninfected population.In conclusion, we observed silent


Imputation of low density (<50K) genotypes to 777K was carried out in either one or two steps. Imputation of ungenotyped parents (n = 37 sires) with four or more offspring to the 50K panel was also assessed. There were 2,946 Braford, 664 Hereford and 88 Nellore animals, from which 71, 59 and 88 were genotyped with the 777K panel, while all others had 50K genotypes. The reference population was comprised of 2,735 animals and 175 bulls for 50K and 777K, respectively. The low density panels were simulated by masking genotypes in the 50K or 777K panel for animals born in 2011. Analyses were performed using both Beagle and FImpute software. Genotype imputation accuracy was measured by concordance rate and allelic R2 was 0.912 and 0.866 for imputation to 50K or to 777K using FImpute, respectively, and 0.890 and 0.826 using Beagle. One and two steps imputation to 777K produced averaged concordance rates of 0.806 and 0.892 and allelic R2 of 0.674 and 0.819, respectively. Imputation of low density panels to 50K, with the exception of 3K, had overall concordance rates greater than 0.940 and allelic R2 greater than 0.919. Ungenotyped animals were imputed to 50K panel with an average concordance rate of 0.950 by FImpute.The average concordance rate using FImpute was 0.943 and 0.921 averaged across all simulated low density panels to 50K or to 777K, respectively, in comparison with 0.927 and 0.895 using Beagle. The allelic R2.FImpute accuracy outperformed Beagle on both imputation to 50K and to 777K. Two-step outperformed one-step imputation for imputing to 777K. Ungenotyped animals that have four or more offspring can have their 50K genotypes accurately inferred using FImpute. All low density panels, except the 3K, can be used to impute to the 50K using FImpute or Beagle with high concordance rate and allelic R Traditional animal breeding methods utilized phenotypic data and relationships among individuals to make informed mating decision to improve traits of economic significance. Recent advances in DNA technology, led to the full sequencing of several species, including cattle  and to tProcedures for imputation of genotypes, a technique that refers to prediction of ungenotyped SNP genotypes, have been the subject of recent studies in some species, such as, dairy cattle ,3, beef The Brazilian cattle industry plays a significant role in the national economy. Brazil has a herd of more than 211 million cattle of which 80% is zebu cattle . HereforThe main objective of this research was to assess accuracy of imputation from lower density SNP panels to genotypes from the Illumina BovineSNP50 and the Illumina BovineHD panels  in Brazilian Braford and Hereford cattle.Animal welfare and use committee approval was not necessary for this study because data were obtained from existing databases.Data was from the Conexão Delta G’s genetic improvement program - Hereford and Braford (Zebu x Hereford) cattle , containing approximately 520,000 animals from 97 farms located in the South, Southeast, Midwest and Northeast regions of Brazil. A total of 683 Hereford and 2,997 Braford animals from these farms were genotyped. Of the genotyped animals, there were 624 Hereford and 2,926 Braford animals genotyped with the Illumina BovineSNP50 panel, and 59 Hereford and 71 Braford animals genotyped with the Illumina BovineHD panel from 17 farms located in the South of Brazil. Data also included 88 Nellore bulls from the Paint Program  genotyped with the Illumina BovineHD panel.−6) [For imputation to the 50K SNP panel, animals genotyped with 777K SNP genotypes had SNPs not contained on the 50K SNP panel removed. This resulted in a population of 3,768 animals genotyped for 49,345 SNPs. Sites were filtered for GenCall score (> = 0.15) ,22, Call−6) ,24. Only−6) ,22, Call−6) ,22, hete−6)  . After the quality control, 218 bulls  and 587,620 SNPs remained.Table For imputation to the 50K SNP panel, the dataset was split into two populations. The imputation population was comprised of all animals born in 2011. The remainder of the population was assigned to the reference population for imputation. This division resulted in 2,735 animals in the reference population when Nellore animals were included and 2,647 when Nellore animals were not included. A total of 963 animals were sorted into the imputation population.Hereford and Braford animals in the reference population included 129 sires born before 2008 and 2,518 animals born between 2008 and 2010. From these 2,518 animals, 3.8% had at least one genotyped offspring.For animals in the imputation population, the 3K, 6K, 8K, 15K and 20K low density SNP panels were created by masking the non-overlapping SNP between the 50K SNP panel and each of these SNP panels. The imputation population included 33 animals with two parents genotyped and 308 animals with one parent genotyped. Moreover, 52% of the imputation animals were offspring of multiple sire matings.The data set for imputation to the 777K SNP panel contained 71, 59 and 88 Braford, Hereford and Nellore animals, respectively. The strategy used to test the imputation was to create three different data sets randomly alternating animals in the reference population and in the imputation population, always keeping the Nellore animals in reference population as the objective was to test the imputation accuracy of Braford and Hereford cattle. Each reference population was composed by 175 animals  and each imputation population had 43 Hereford and Braford animals. For animals in the imputation population the 3K, 6K, 8K, 15K, 20K, 50K, 90iK and 90tK SNP panels were created by masking non-overlapping SNP from 777K SNP panel.All panels, but one, were commercial panels: Illumina Bovine3K (3K), Illumina BovineLD (6K), Illumina BovineSNP50 (50K) and Illumina BovineHD (777K) panels , Beef LD GGP (8K), Indicus LD GGP 20K), GGP Taurus HD (90tK) and GGP Indicus HD (90iK) panels   were selected from the 50K SNP panel using high minor allele frequency, low linkage disequilibrium, and location (approximately evenly spaced between two SNPs in the 8K SNP panel) as selection criteria. The best possible threshold values to meet the three criteria were a minor allele frequency greater than 0.23 and a linkage disequilibrium, as measured by rFor imputation to the 50K SNP panel, four different scenarios were explored as follows: including Nellore genotypes in the reference population and either including pedigree information (NE-P) or not including pedigree information (NE-NP); not including Nellore genotypes in the reference population and either including pedigree information (NNE-P) or not including pedigree information (NNE-NP).For imputation to the 777K SNP panel, a third set of Hereford and Braford bulls were imputed in four different scenarios: including Nellore genotypes and pedigree information in the reference population (NE-P) or including Nellore genotypes and not including pedigree information in the reference population (NE-NP). Each of these two scenarios was carried out in one or two steps. Two-step imputation was carried out only for panels with density less than 50K SNP. Two-step imputation involved: 1) in the first step, the animals genotyped with 3K, 6K, 8K, 15K and 20K SNP panels were imputed to the 50K SNP panel using in the reference population all the animals genotyped with the 50K SNP panel; 2) in the second step, all the animals imputed to the 50K SNP panel were then imputed to the 777K SNP panel using as reference two-thirds of the Hereford and Braford and all Nellore bulls genotyped with the 777K SNP panel. One-step imputation was performed by imputing from the simulated low density panels directly to the 777K SNP panel.2, which corresponds to the square of the correlation between the number of minor alleles in the imputed genotype and the number of minor alleles in the original genotype [Imputation accuracy of above scenarios was assessed by concordance rate (CR), which corresponds to the proportion of genotypes correctly imputed, and by allelic Rgenotype .There were thirty imputation scenarios from low density panels to the 50K SNP panel. Twenty-four scenarios were examined for imputation from low and medium density panels to 777K SNP panel and thirty scenarios were used to assess differences in imputation accuracy in one or two steps Table .Table 3Imputation was carried out by FImpute v.2.2  and BeagImputation methods can be based on linkage disequilibrium information between markers in the population, but also can use the inheritance information within family. Beagle software is based on linkage disequilibrium between markers in the population and uses a Hidden Markov model  for infe2 of each scenario. An arcsine square root [2 to normalize the residuals.Analysis of variance was carried out using the GLM procedure in SAS version 9.2  to compare the average CR and allelic Rare root  transforOf the 3,698 animals genotyped with the 50K SNP panel, ~24% had sire and/or dam genotyped and ~65% had at least one parent unknown in the pedigree. With respect to the animals genotyped with the 777K SNP panel, ~15% had sire and/or dam genotyped and ~35% had at least one parent unknown. Table 2 for imputation to 50K and 777K SNP panels.Table 2 between the two algorithms and between pairs of simulated low density panels, as well as a significant algorithm by panel interaction (P < 0.05). However, there were no significant differences (P > 0.05) in CR and allelic R2 between scenarios (Table There were significant differences (P < 0.05) in CR and allelic Ros Table .Table 62 of 0.962, 0.109 and 0.175 points higher than the 3K SNP panel, respectively  when compared to denser panels , with FImpute being consistently more accurate. Imputation accuracy for 8K and 20K SNP panels were not significantly different using Beagle (P > 0.05) with respect to CR and allelic R2 (Table 2 (>0.967) were obtained using the 15K SNP panel and FImpute.The non-commercial 15K SNP panel resulted in the highest imputation accuracy of the low density panels with an overall CR of 0.973 and allelic RAn important measurement of imputation success is the number of animals imputed with modest accuracy (assumed <0.950 CR here). Using the 15K SNP panel resulted in 93% and 83% of the animals being imputed with a CR above 0.950  for FImpute and Beagle, respectively, while using the 3K SNP panel as the low density panel resulted in only 6.3% and 0.8% of animals above this accuracy threshold using FImpute and Beagle, respectively. The results for the other panels ranged between 62% and 70% using FImpute and between 40% and 48% using Beagle  for the 3K SNP panel, from either FImpute or Beagle, were lower than all other panels with CR values over all BTAs at or below 0.900. All other panels produced CR above 0.930 for all chromosomes. Imputation accuracy was found to be relative to chromosome length with the highest CRs obtained for BTA1 while the lowest CRs were obtained for BTA28 in all scenarios and both algorithms, however little difference was seen across the genome  to the 50K SNP panel was calculated for three different classes of minor allele frequency (MAF) . For the MAF class <0.01 the average CR was close to 1.00 for all panel densities. For SNPs with MAF 0.01-0.05 and >0.05 the average CRs ranged similarly from 0.84 to 0.97, depending on the panel density  (Table There were significant differences (P < 0.05) in CR and allelic R2 of 0.866, while Beagle yielded an average CR of 0.895 and allelic R2 of 0.826  and the lowest CR and allelic R2 with the 3K SNP panel . For the other panels, CR was between 0.898 and 0.952 and allelic R2 was between 0.829 and 0.919 (Table 2 for imputation to the 777K SNP panel (P < 0.05)  when compared to denser panels , with FImpute resulting in consistently higher accuracy of imputation.Using FImpute resulted in an overall average CR of 0.921 and allelic R 2 Table . The higThe distributions of animals in high classes of CR varied between FImpute and Beagle. For FImpute, the proportion of animals imputed above a CR of 0.95 ranged from 12.8% for the 3K SNP panel to 73.6% for the 90iK SNP panel. For the other panels, the proportion of animals was between 20% and 48% . The interaction between number of steps and low density panel showed that the difference between CR and allelic R2 from one to two steps imputation was larger for sparse panels  when compared to denser panels  to imputation in a one-step both when measured by CR and allelic Ros Table . The int2 was 69%, 21% 22% 9% and 4% for 3K, 6K, 8K, 15K and 20K SNP panels, respectively.The relative increase in CR for the two-step imputation with respect to the one-step imputation was 27%, 12%, 11%, 5% and 2% for 3K, 6K, 8K, 15K and 20K SNP panels, respectively, and the relative increase in allelic RThe average CR for imputation from the alternative low density panels  to the 777K SNP panel was calculated for three different classes of MAF . For the MAF class <0.01 the average CR was close to 0.99 for all panel densities, for MAF class 0.01-0.05 and >0.05 the average CRs ranged from 0.84 to 0.97 and from 0.65 to 0.96, respectively, depending on the panel density . Preliminary results obtained by Sargolzaei et al.  and BerrThese results were similar to the ones reported by Berry et al.  studyingAll low density panels, except the 3K SNP panel, can be used to impute to the 50K SNP panel with average concordance rates higher than 0.940. The customized 15K SNP panel yielded the highest percentage of animals with concordance rate above 0.950 of all the low density panels studied.The 50K, 90iK and 90tK SNP panels can be used to impute to the 777K SNP panel with average concordance rates higher than 0.940. A two-step imputation is recommended for lower density panels, making use of all available intermediate density panel genotypes.FImpute outperformed Beagle in all scenarios for imputation to both the 50K and to the 777K SNP panels both in terms of accuracy and computing time required.Ungenotyped animals that have four or more offspring and do not have available biological material to carry out genotyping may have their 50K SNP panel genotype inferred with an average concordance rate of 0.950 in the Hereford/Braford population analyzed.


Hospital acquired infection (HAI) prevalence surveys have been conducted in French healthcare facilities (HCF) since 1996. Overall HAI prevalence rate remained steady around 5.0% in France from 2006 to 2012. A decreased by 10.8% was found when a multilevel analysis was applied and contrasting trends were shown: no significant change for short stay hospitalization (from 5.3% to 5.6%) whereas a significant decrease by 21% was observed in the others. In Franche-Comté (FC), from 2006 to 2012, an unexpected increasing HAI prevalence trend by 17.3% (from 5.2% to 6.1%) was observed.To assess if the FC HAI prevalence trend is in line with the national trend.All adult patients in the 10 FC HCF that have participated every year from 2006 to 2013 were enrolled. The outcome was patient infected status. Sets of confounding factors were considered at 2 levels: patient and HCF. Almost factors were dichotomous: sex, immune-compromised status, exposure to invasive device and to surgical procedure, type of stay. Dummy variables were generated for ordinal variables  taking the lowest category as the reference group and year as a continuous variable. Multilevel analysis was applied using the Poisson regression. Statistical analysis was performed using MlWin software.95CI[1.01 – 1.06], p=0.01). For short stay, the linear time trend wasn’t statistically significant . To be exposed to invasive device  and to have been exposed to surgical procedure  were the only statistically significant risk factors. By contrast, in other type of stay, all studied factors were statistically significant as the linear trend also .From 2006 to 2013, 20,629 patients were enrolled. The HAI prevalence rate increased from 4.5% to 6.3% and a crude linear time trend was statistically significant (RR=1.03 FC HAI prevalence trend doesn’t match the national one. The crude linear time trend was statistically significant. To be hospitalized in short stay was associated to a lower risk of HAI whereas to be hospitalized in other type stay was at higher risk.None declared.


Motorcycle users involved in crashes are likely to die or be severely injured due to high frequency of head, chest and leg injuries. We carried out a descriptive cross sectional study to determine crash characteristics and injury patterns among motorcycle users attending Kitale district hospital, Kenya.st August 2013 and 31stOctober 2013. Data collection was done using a pre-tested, coded questionnaire. Frequencies mean (SD) and chi-square was employed in the analysis. Analysis was done using SPSS V.20. Results were considered significant at α = 0.05.Motorcycle trauma patients were recruited between 12=129.936, p < 0.001). Head injury patients were assessed as having Glasgow coma scale (GCS) of 70% 9-12, 26% GCS of 13-15 and 7% GCS of 3-8. Injuries sustained by victims included head and neck injury 40%, lower extremity injury 39.9% and chest injury 8.2%. Riders without helmets during the crash sustained head injuries .Motorcycle trauma patients formed 39.4% of all road traffic injuries. Males constituted 69.8%, females 30.2% and mean age was 30(±13) years. Riders accounted for majority of injury patients (45%), passengers (38.8%) and pedestrians (15.9%). Mechanism of motorcycle crash was involving motorcycle versus vehicle (45.6%). Riders suffered severe injuries compared to passengers (χHead injuries and lower extremity injuries accounted for the major proportion of injuries sustained by motorcycle users. Non helmet use was associated with increased risk of head injuries. Morbidity can be mitigated by encouraging use of protective gear like helmets. Globally it is estimated that, 1.2 million people are killed in road crashes each year and as many as 50 million are injured , 4. The st August 2013 and 31st October 2013. All victims of commercial motorcycle crash injuries presenting at the accident and emergency department were eligible for the study. At presentation, patients or their conveyers were interviewed by research assistants according to the details provided on a pro-forma. The data collected were patient's bio data, the injury sustained, mechanism of the crash injury, pre hospital transportation, body region injured, radiological findings, setting of the crash, condition of the road, collision type and use of helmet. The personal status during the crash was identified whether he/she was the rider, passenger and pedestrian. The fate of the subject whether discharged in good condition, admitted to the wards, referred or died was documented. Using the Fischer's exact test [This was a descriptive cross-sectional study of patients with commercial motorcycle crash injuries of all age groups and gender presenting at the Accident and Emergency (A&E) department of Kitale level IV District Hospital. Kitale town is located at high Agricultural potential area of Trans-Nzoia County with an estimated population of 200,000. Kitale level IV district hospital provides Accident and Emergency services and its Government sponsored. Most patients seek health care services from the Government hospital due to lower charges as compared to the private hospitals. Trauma patients are first resuscitated and managed at the A&E Department according to the Advanced Trauma Life Support (ATLS) principles and then admitted to the admitting surgical firm. The study population comprised victims of commercial motorcycle crashes presenting at the Accident and Emergency department between 1act test  the mini21-α/2 PQ/d2n = Z21-α/2 = standard normal deviate within 95% confidence interval (1.96) P = assumed proportion of commercial motorcycle crash injuries among patients attending, Kitale level IV District Hospital (50%).Where n = required sample size, α = level of significance (0.05), Q = 1-p, Zd = level of precision at 5% , n = (1.962×0.5×0.5) ÷ 0.052 n =384, Sample size = 384But since the sampling frame was <10,000, the sample size was adjusted using the formula by fishers 1991, n= n/ (1 +n/N)Where: n= initial sample size, N = sampling frame, n = new sample size, n= 384/ (1 +384/1800), = 317 motorcycle patients were required for the study.Commercial Motorcyclists and passengers were eligible for inclusion in the study if they presented to the accident and emergency department within 24 hours of the Motorcycle crash injury. Motorcycle crash victims who came unconscious were also enrolled in this study after consent was obtained from their relative or from themselves after gaining conscious either in ICU or in the ward. Two trained research assistant were stationed in the accident and emergency department who interviewed patients and did data entry. Diagnosis was reached through clinical history, examination and radiological investigations. Topographic locations of injuries were then entered in the structured questionnaire. Information about diagnosis, registration number was retrieved from patient's file and admission register books. Data cleaning and validation was performed using SPSS version 20. Descriptive statistics such as mean, standard deviation, range and frequency proportions was performed. Pearson's chi square was used to test for the significance of association between dependent variable and independent variables. The level of statistical significance was set at P < 0.05. Binary logistic regression was used to adjust for confounding. Ethical approval was granted by the Kenya medical research institute ethics committee. The scientific steering committee of Kenya medical training institute also approved the study. Consent to carry out the study was also obtained from the administrators of the participating hospital.During the study period 942 cases of road traffic injuries were seen at the Accident and Emergency department. Commercial Motorcycle traffic injuries accounted for 39.4% of all road traffic injuries. The mean age of the patients was 30.7 years with a standard deviation 0f 13. The youngest reported age was 3 years and the oldest was 80 years, with a range of 77 years. Majority of the patients were males 259 (69.8%) while females were 112 (30.2%), with a male to female ratio of 2.3:1. Most of the injured patients were riders 167 (45%), passengers injured accounted for 144 (38.8%), while pedestrians accounted for 59 (15.9%). Majority of the riders had attained primary level of education 106 (44%), while 92 (38.2%) of passengers and 43 (17.8%) of pedestrians had basic level of education . Majorit2=129.936, p < 0.001)  (Among the riders 49 (29.3%) suffered severe injuries as compared to passengers 9 (6.2%) and pedestrians 2 (3.4%). Passengers suffered moderate injuries 127 (88.2%) as compared to riders 106 (63.5%) and pedestrians 25 (42.4%). Pedestrians suffered minor injuries 32 (54.2%), riders 13 (7.7%) and passengers 8 (5.6%). This was statistically significant (χ< 0.001) . On arri< 0.001) . Majorit< 0.001) .In this study the prevalence of Commercial Motorcycle crashes was in agreement with studies conducted in other developing countries. The reported prevalence of motorcycle injuries varies around the world, from 22.8% in China  to as hiThe commonest anatomical/site of injury were head and neck and lower extremities. The findings are similar to a study in Tehran, which documented that the commonest musculoskeletal injury was fracture of the tibia comprising almost 50% of cases . PreviouMotorcycle crash is a major cause of road traffic injury among victims attended to at Kitale level IV district hospital. Male riders constituted the single largest risk group. Common cause of motorcycle crash was collision with a vehicle. Head injuries and lower extremity injuries accounted for major proportion of injuries sustained. Non helmet use was associated with increased risk of severe head injuries. Morbidity can be mitigated by use of protective gear like helmets and enforcement of traffic regulations.


We conducted this prospective study to evaluate the prognostic significanceof uterine and ovarian artery Doppler velocimetry in clomiphene citrate (CC) cycles.A total of 80 patients with unexplained infertility were given100 mg/day of CC from day 3 to day 7 of their cycles in this current prospective study. Oncycle day 3, before administration of CC, each patient underwent Doppler transvaginal ultrasonography. The Doppler velocimetries of the right and left uterine and ovarian arteries wererecorded and analyzed in association with demographic and clinical parameters.TheThere were 6 out of 80 patients who became pregnant, the overall pregnancyrate in this population was 7.5% for the current study. The cases were divided into twogroups according to whether they became pregnant or not. Demographic characteristicsshowed no statistically significant differences between these groups (p>0.05). However,the duration of infertility did show statistically significant differences between the groups.Doppler velocimetry was not statistically significantly different between the two groups.Doppler velocimetry of the uterine and ovarian arteries is not a factor in theprognosis for pregnancy in CC cycles. Clomiphene citrate (CC) is an agent that hasbeen used since the 1960s for ovulation induction.In appropriately selected anovulatory women, CCsuccessfully induces ovulation in about 70-80% ofcases; among these women the overall cycle fecundabilityis approximately 15% . CC actsFactors that affect pregnancy rates in CC cycleshave been reported in previous studies. The agesof the women, longer duration times of their infertilityand decreased ovarian reserves have been describedas factors that indicate poor prognosis forpregnancy in CC cycles . The diaIn addition, Doppler velocimetry studies havebeen conducted to evaluate the changes in bloodflow in the uterus and ovaries during the normalmenstrual cycle , 8. Ng eThe current study evaluated the effectiveness ofDoppler velocimetries of the uterine and ovarianarteries as a predictor of successful pregnancy inCC cycles.This interventional, cross-sectional study wasundertaken from May 2013 to June 2013 in theDepartment of Obstetrics and Gynecology, Divisionof Infertility and Gynecological Endocrinologyat Dr. Zekai Tahir Burak Women’s HealthEducation and Research Hospital. This is a tertiaryreferral research hospital located in the central regionof Turkey. It is a government-supported hospitalwhere most of the health services are offeredfree of charge.The study was designed according to the HelsinkiDeclaration  and all Women who had had unexplained infertility (primaryor secondary) for at least one year were includedin the study. A total of 80 women receivedoral CC, 100 mg daily, from day 3 to day 7 of theirmenstrual cycles. All of the cases received regularultrasound monitoring for follicle growth andET through transvaginal ultrasonography on day12 of their cycles and again every other day untilthe leading follicle reached 17-23 mm, triggeredby hCG. Transvaginal Doppler velocimetry waveformswere also obtained from the bilateral uterineand ovarian arteries of each patient for analysis.The ultrasound examinations, performed on day 3of the menstrual cycle while the patients were inthe lithotomy position used color Doppler sonographywith a 7.5 MHz pulse endovaginal Dopplersystem for blood flow analysis . The women’s bladders were emptied beforetheir examinations. The uterine artery was locatedlaterally to the isthmic region of the uterusand the ovarian artery was found at the lateral poleof the ovary near the infundibulopelvic ligament.The following factors that affected patients’ risklevels were recorded: age, infertility type, durationof infertility, gravidy, parity, number of pregnancylosses, number of living children, ET, cycle day 3serum FSH, LH and estradiol (E2) levels, uterineand ovarian artery Doppler velocimetries, numberof antral follicules, dominant follicle sizes andpregnancy. The Doppler velocimetries measuredwere the right side uterine and ovarian artery pulsatilityindex (PI) and resistance index (RI) in additionto the left side uterine and ovarian artery PIand RI.The cases were divided into two groups accordingto whether patients achieved pregnancy or not.At the end of the study, a total of 6 (7.5%) patientswere pregnant. Pregnancy was determined by positiveβ-hCG and a visible intrauterine gestationalsac.2), Mann-Whitneyand independent sample t tests where appropriate.The sample size was determined according to theresults of the central limit theorem  unless otherwise indicated. The normaldistribution of the variables was analyzed by theKolmogorov-Smirnov test. Statistical comparisonwas carried out by Chi-square . However, the durations of infertilityof the two groups showed statisticallysignificant differences (p<0.007). The basalfollicle numbers were 6.66±3.72 for the rightovary and 6.75±3.15 for the left ovary in thegroup that achieved pregnancy and 6.33±4.08(right ovary) and 6.67±3.17 (left ovary) for thegroup that did not. The mean diameters of theleading follicle on the day that hCG was administeredfor the group that achieved pregnancywas 16.50±6.44 mm and for the group that didnot achieve pregnancy it was 15.16±4.51 mm,for the right ovary. For the left ovary, this valuewas 15.16±7.30 mm in the group that achievedpregnancy versus 14.77±4.82 mm in the groupthat did not achieve pregnancy (p>0.05).The measurement of Doppler velocimetry onday 3 of the cycle was as follows: the right sideuterine artery mean (min-max) was PI: 3.33 ±2.40, RI: 1.14±0.59, the right side ovarian arterywas PI: 2.30±1.97, RI: 1.11±0.87; the leftside uterine artery was PI: 3.11±1.91, RI: 1.21±0.64 and the left side ovarian artery was PI:3.29±2.31, RI: 1.10±0.72.In this study we examined 80 women who hadunexplained infertility for at least one year withthe intent to evaluate the uterine and ovarian arteryDoppler velocimetries as predictors of a successfullyachieved pregnancy. The patients receivedoral CC, 100 mg daily, from day 3 to day 7 of theirmenstrual cycles. At the end of the study, 6 (7.5%)of the patients had achieved pregnancy. We dividedthe cases into two groups based on whether the patienthad achieved pregnancy or not and found thatthe demographic and clinical parameters showedno statistically significant differences betweenthe groups. However, the differences between thegroups in terms of the durations of infertility werestatistically significant. The Doppler velocimetryvalues also showed no statistically significant differencesbetween the groups.Doppler velocimetry of the uterine, spiral andovarian arteries has been previously investigatedin different types of cases, various phases ofthe menstrual cycle, ovulation induction and inearly pregnancy. First, Kupesic and Kurjak reportedNakai et al.  studied In addition, Ragni et al.  evaluateIn a previous study, Ng et al.  reportedBaruah et al.  designedWe believe that Doppler velocimetries of theuterine and ovarian arteries are not prognostic factorsfor pregnancy in CC cycles.


T2-weighted enhancement depicts the myocardial area at risk (AAR) associated with coronary occlusion. However, the severity of blood flow abnormality required to cause a detectable elevation in myocardial T2 is unknown. The aim of this study was to use microspheres to determine the severity of reduction in myocardial blood flow that results in visually detectable T2 weighted enhancement.Surface coil intensity corrected T2 prepared SSFP at 1.5T was performed after 2 hours of coronary occlusion followed by 4 hours of reperfusion in a canine model. Myocardial blood flow during ischemia was determined by administering microspheres. A mid-ventricular short axis slice of the heart was divided into 16 transmural sectors for microsphere analysis. MR images were matched to the pathological slices at the sector level using papillary muscles and RV insertion as landmarks. ROIs delineated T2-enhanced and remote regions of the MR images and measurements were compared with microsphere blood flows. Results were reported as median (interquartile range [IQ]) and compared using the signed Wilcoxon rank test. Each T2-prepared sector was classified as bright (AAR) or normal (remote) by 2 independent readers and compared with absolute microsphere blood flow and flow relative to remote myocardium. ROC analyses were performed to find the thresholds of absolute and relative blood flow reduction needed to detect T2 enhancement in the sector based analysis.In ROI analysis (n = 20), SNR in the AAR was 14.6 +/- 5.7 and CNR of AAR vs. remote regions was 5.7 +/- 2.3. Median blood flow in remote myocardium was 1.15 ml/min/g (IQ 0.73-1.74) and in the AAR 0.072 ml/min/g (IQ 0.020-0.22), p < 0.0001. The blood flow threshold that best separated increased T2 signal intensity from normal was 0.44 ml/min/g Figure . In a seA relative reduction in blood flow 24% lower than remote myocardium was the best threshold discriminating detectable T2 enhancement in the area at risk. An absolute blood flow reduction below about 0.44-0.50 ml/min/g also predicted T2 enhancement.Funded by the Intramural Research Program of the National Heart, Lung, and Blood Institute of The National Institutes of Health.


Introduction. Maximum diameter of an abdominal aortic aneurysm (AAA) is the main indication for surgery. This study compared colour duplex ultrasound (CDU) and computed tomography (CT) in assessing AAA diameter. Patients and Methods. Patients were included if they had both scans performed within 90 days. Pearson's correlation coefficient, paired t-test, and limits of agreement (LOA) were calculated for the whole group. Subgroup analysis of small (<5.0 cm), medium (5.0–6.5 cm), and large (>6.5 cm) aneurysms was performed. A P value of <0.05 was considered statistically significant. Results. 389 patients were included, giving 130 pairs of tests for comparison. Excellent correlation was in the whole group (r = 0.95) and in the subgroups . Small LOA between the two imaging modalities was found in all subgroups. Conclusion. Small aneurysms can be accurately measured using CDU. CDU is preferable for small AAAs, but cannot supplant CT for planning aortic intervention. Annual abdominal aortic aneurysm (AAA) maximum aneurysm diameter is the main indication for the timing of elective repair. The modality of choice to determine the maximum diameter prior to intervention is computed tomography (CT). CT provides a detailed anatomical image with 3-dimensional reconstruction, thus allowing measurement of the maximal aortic diameter perpendicular to the central line of flow . CT is cColour duplex ultrasound (CDU) is a safe modality for the surveillance of patients with small AAA's , 6. It iThis study aimed to compare the two imaging modalities of CDU and CT in assessment of the maximum aneurysm diameter in patients under surveillance for AAA.Approval was obtained from the hospital ethics committee for the study. All patients attending the vascular laboratory of the Mater Misericordiae University Hospital (MMUH) between the 1st of January 2007 and the 31st of December 2009 were recruited if they had a CDU and a CT scan for assessment of their AAA within 90 days of each other.All CDU scans were performed in the supine position by a qualified vascular technologist proficient in abdominal imaging using one of 3 machines, a Siemens Sequoia 512, a Siemens S2000, or a Phillips IU22. All CDU scans were performed using a wideband curvilinear transducer. The maximum anterior to posterior (AP) wall diameter and the maximum transverse wall diameter were recorded with the greater of the two measurements being taken as the maximum aneurysm diameter and used for comparison in this study. The outer-to-outer diameter was used for the definition of AAA diameter.All CT scans were carried out in the Radiology Department of the MMUH following their standard protocol for abdominal imaging. The maximum aneurysm diameter documented on the final report by a consultant radiologist was used for comparison in this study. The outer-to-outer diameter was also used as the diameter definition for CT scans, to ensure equality of definition in comparison.Continuous variables were expressed as mean (± SD). Correlation between the CDU and CT was performed using Pearson's coefficient correlation analysis. Limits of agreement (LOA) were also performed with the method described by Bland and Altman . LOA com t-test, and LOA were calculated for the group of patients as a whole. Patients were then divided into three subgroups small, medium, and large aneurysms  were male and twenty-seven (21.4%) were female with an overall mean age of 76.1 (± 7.1) years. The mean male age was 76.1 (± 6.5) and the mean female age was 76.2 (± 9.0).Entire Group (n = 130). Mean AAA diameter on CDU was 5.4 (± 1.0) cm and on CT was 5.4 (± 1.0) cm. Correlation was excellent .Small Aneurysms (AAA < 5.0 cm). Twenty-nine pairs of scans were in this subgroup. Mean AAA diameter on CDU was 4.2 (± 0.68) cm and 4.2 (± 0.58) cm on CT (P = 0.4). Correlation was excellent (r = 0.94) for aneurysms less than 5.0 cm.Medium Aneurysms (AAA 5.0>–<6.5 cm). Eighty-eight (69.8%) pairs of scans were in this subgroup. Mean aneurysm size on CDU was 5.5 (±0.39) cm and was 5.0 (± 0.43) cm on CT (P = 0.2). Correlation for this group was good (r = 0.69).Large Aneurysms (>6.5 cm). Thirteen pairs of scans were in this subgroup. Mean AAA diameter on CDU was 7.4 (± 0.83) cm and 7.5 (± 0.79) cm on CT (P = 0.1). Correlation was found excellent (r = 0.96).The limits of agreement were found to be between −0.46 and 0.47, within the acceptable range.The limits of agreement were found to be between −0.68–0.59, within the acceptable range.The limits of agreement were found to be between −0.55–0.35, within the acceptable range.This study evaluated the accuracy of CDU in assessing maximum AAA diameter compared to the gold standard method of CT. The two modalities demonstrated a large overall degree of correlation and a strong correlation achieved in all three subgroups by size, verifying that measurement of aneurysm size can be accurately measured by either imaging modality. LOA analysis of both the overall cohort and the subgroups demonstrated that despite achieving excellent correlation and small LOA between the two imaging modalities in all groups, the small aneurysm groups (<5 cm) were found to have better agreement with 95% of the differences in the two measurements falling between −0.46 and 0.47.Discordance in measurements between various imaging modalities when measuring the maximal AAA diameter has been reported previously. Several authors have reported that maximal AAA diameter on CT is smaller than that obtained on duplex, while Meier documented that AAA diameter with ultrasound is usually larger than CT –11. In aThe discordance between imaging modalities has been explained by the variation in techniques used to determine maximum aneurysm diameter, together with the presence of interobserver error. The definition of maximum diameter in this study for both modalities was outer-to-outer diameter. Inner-to-inner diameters were not measured in this study, and similar correlations are likely to be obtained, although it would be an interesting further study that could be performed. The United Kingdom Small Aneurysm Trial (UKSAT participants) used the maximal anterior to posterior wall measurements as obtained by ultrasound and recommended that surgical repair should take place on aneurysms greater than 5.5 cm in AP measurements . This stThe high degree of correlation achieved in this study may be explained by the improved greyscale resolution and harmonic imaging achieved by the currently available ultrasound machines. Duplex colour ultrasound was used in this study, as it is local protocol to do so, for the purposes of identifying any other haemodynamically significant coexisting occlusive diseases. However, B-mode sonography would provide equivalent measurements and correlations with CT, since it is the B-mode aspect of the scan that provides the measurements. Sprouse demonstrated an overall high correlation of 0.70 compared to the overall correlation of 0.95 found in this study [AAA's less than 5 cm in diameter can be accurately measured using CDU. On the basis of these results, it is reasonable to suggest that CDU is the surveillance tool of choice for small AAAs, but cannot hope to supplant CT as the definitive planning tool prior to aortic intervention.