The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal ...microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.
An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.
Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.
FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
Abstract Background & aims Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to review the literature and provide specific, updated ...recommendations for eradication therapy in adults. Methods A systematic literature search identified studies on H. pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. Results Because of increasing failure of therapy, the consensus group strongly recommended that all H. pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant non-bismuth quadruple therapy (proton pump inhibitor, PPI + amoxicillin + metronidazole + clarithromycin, PAMC), and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBMT). PPI triple therapy (PPI + clarithromycin and either amoxicillin or metronidazole) was restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin, PAL). Rifabutin regimens should be restricted to patients who fail at least 3 prior options. Conclusions Optimal treatment of H. pylori requires careful attention to local antibiotic resistance and eradication patterns. Quadruple therapies PAMC or PBMT should play a more prominent role in H. pylori eradication and all treatments should be given for 14 days.
Two new species within the Anopheles gambiae complex are here described and named. Based on molecular and bionomical evidence, the An. gambiae molecular "M form" is named Anopheles coluzzii Coetzee & ...Wilkerson sp. n., while the "S form" retains the nominotypical name Anopheles gambiae Giles. Anopheles quadriannulatus is retained for the southern African populations of this species, while the Ethiopian species is named Anopheles amharicus Hunt, Wilkerson & Coetzee sp. n., based on chromosomal, cross-mating and molecular evidence.
An area of great interest in evolutionary genomics is whether convergently evolved traits are the result of convergent molecular mechanisms. The presence of queen and worker castes in insect ...societies is a spectacular example of convergent evolution and phenotypic plasticity. Multiple insect lineages have evolved environmentally induced alternative castes. Given multiple origins of eusociality in Hymenoptera (bees, ants, and wasps), it has been proposed that insect castes evolved from common genetic "toolkits" consisting of deeply conserved genes. Here, we combine data from previously published studies on fire ants and honey bees with new data for Polistes metricus paper wasps to assess the toolkit idea by presenting the first comparative transcriptome-wide analysis of caste determination among three major hymenopteran social lineages. Overall, we found few shared caste differentially expressed transcripts across the three social lineages. However, there is substantially more overlap at the levels of pathways and biological functions. Thus, there are shared elements but not on the level of specific genes. Instead, the toolkit appears to be relatively "loose," that is, different lineages show convergent molecular evolution involving similar metabolic pathways and molecular functions but not the exact same genes. Additionally, our paper wasp data do not support a complementary hypothesis that "novel" taxonomically restricted genes are related to caste differences.
Initial performance assessment of CALIOP Winker, David M.; Hunt, William H.; McGill, Matthew J.
Geophysical research letters,
October 2007, Letnik:
34, Številka:
19
Journal Article
Recenzirano
Odprti dostop
The Cloud‐Aerosol Lidar with Orthogonal Polarization (CALIOP, pronounced the same as “calliope”) is a spaceborne two‐wavelength polarization lidar that has been acquiring global data since June 2006. ...CALIOP provides high resolution vertical profiles of clouds and aerosols, and has been designed with a very large linear dynamic range to encompass the full range of signal returns from aerosols and clouds. CALIOP is the primary instrument carried by the Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite, which was launched on April 28, 2006. CALIPSO was developed within the framework of a collaboration between NASA and the French space agency, CNES. Initial data analysis and validation intercomparisons indicate the quality of data from CALIOP meets or exceeds expectations. This paper presents a description of the CALIPSO mission, the CALIOP instrument, and an initial assessment of on‐orbit measurement performance.
We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). ...Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = -0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.
Objectives To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected ...individuals.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.Eligibility criteria for selecting studies Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥2 years.Main outcome measures Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.Results The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I2=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.Conclusions These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.
To examine the effect of changes in utilization and advances in cross-sectional imaging on radiologists' workload.
All computed tomography (CT) and magnetic resonance imaging (MRI) examinations ...performed at a single institution between 1999 and 2010 were identified and associated with the total number of images for each examination. Annual trends in institutional numbers of interpreted examinations and images were translated to changes in daily workload for the individual radiologist by normalizing to the number of dedicated daily CT and MRI work assignments, assuming a 255-day/8-hour work day schedule. Temporal changes in institutional and individual workload were assessed by Sen's slope analysis (Q = median slope) and Mann-Kendall test (Z = Z statistic).
From 1999 to 2010, a total of 1,517,149 cross-sectional imaging studies (CT = 994,471; MRI = 522,678) comprising 539,210,581 images (CT = 339,830,947; MRI = 199,379,634) were evaluated at our institution. Total annual cross-sectional studies steadily increased from 84,409 in 1999 to 147,336 in 2010, representing a twofold increase in workload (Q = 6465/year, Z = 4.2, P < .0001). Concomitantly, the number of annual departmental cross-sectional images interpreted increased from 9,294,140 in 1990 to 94,271,551 in 2010, representing a 10-fold increase (Q = 8707876/year, Z = 4.5, P < .0001). Adjusting for staffing changes, the number of images requiring interpretation per minute of every workday per staff radiologist increased from 2.9 in 1999 to 16.1 in 2010 (Q = 1.7/year, Z = 4.3, P < .0001).
Imaging volumes have grown at a disproportionate rate to imaging utilization increases at our institution. The average radiologist interpreting CT or MRI examinations must now interpret one image every 3-4 seconds in an 8-hour workday to meet workload demands.
This paper presents an extension of the Pipe-in-Pipe (PiP) model for calculating vibrations from underground railways that allows for the incorporation of a multi-layered half-space geometry. The ...model is based on the assumption that the tunnel displacement is not influenced by the existence of a free surface or ground layers. The displacement at the tunnel–soil interface is calculated using a model of a tunnel embedded in a full space with soil properties corresponding to the soil in contact with the tunnel. Next, a full space model is used to determine the equivalent loads that produce the same displacements at the tunnel–soil interface. The soil displacements are calculated by multiplying these equivalent loads by Green׳s functions for a layered half-space. The results and the computation time of the proposed model are compared with those of an alternative coupled finite element–boundary element model that accounts for a tunnel embedded in a multi-layered half-space. While the overall response of the multi-layered half-space is well predicted, spatial shifts in the interference patterns are observed that result from the superposition of direct waves and waves reflected on the free surface and layer interfaces. The proposed model is much faster and can be run on a personal computer with much less use of memory. Therefore, it is a promising design tool to predict vibration from underground tunnels and to assess the performance of vibration countermeasures in an early design stage.
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