A STUDY OF ION KINETIC-ENERGY SPECTROMETRY OF ORTHO-DICHLORO, META-DICHLORO AND PARA-DICHLORO BENZENE DOUBLY CHARGED IONS [C6H4CL2]2+ AND [C6H3CL]2+ IN GAS-PHASE

The unimolecular Charge separation reactions of the doubly charged ions [C6H4Cl2]2+, [C6H3Cl]2+ produced in the ion source by electron impact from o-, m-, and p-dichloro benzene have been studied using mass analysed ion kinetic energy spectrometry. The values of kinetic energy releases (T) can be calculated from the energy dispersion of product ions. As T essentially reflects the release of coulombic energy, which can be used to calculate the approximate distances R between the two charges immediately before decomposition of the ions. From these data, some structural information about transiton states could be provided. The ECID and CID processes of above doubly charged ions, have also been studied. We found that the CID reactions of (C6H4Cl2)2+ could be used to distinguish three dichloro benzene isomers.

Meta-stable memory in an artificial immune network

Neal, M., Meta-stable memory in an artificial immune network, Proceedings of the 2nd International Conference on Artificial Immune Systems {ICARIS}, Springer, 168-180, 2003,LNCS 2787/2003

Auriculotherapy for pain management: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Side-effects of standard pain medications can limit their use. Therefore, nonpharmacologic pain relief techniques such as auriculotherapy may play an important role in pain management. Our aim was to conduct a systematic review and meta-analysis of studies evaluating auriculotherapy for pain management. DESIGN: MEDLINE,(®) ISI Web of Science, CINAHL, AMED, and Cochrane Library were searched through December 2008. Randomized trials comparing auriculotherapy to sham, placebo, or standard-of-care control were included that measured outcomes of pain or medication use and were published in English. Two (2) reviewers independently assessed trial eligibility, quality, and abstracted data to a standardized form. Standardized mean differences (SMD) were calculated for studies using a pain score or analgesic requirement as a primary outcome. RESULTS: Seventeen (17) studies met inclusion criteria (8 perioperative, 4 acute, and 5 chronic pain). Auriculotherapy was superior to controls for studies evaluating pain intensity (SMD, 1.56 [95% confidence interval (CI): 0.85, 2.26]; 8 studies). For perioperative pain, auriculotherapy reduced analgesic use (SMD, 0.54 [95% CI: 0.30, 0.77]; 5 studies). For acute pain and chronic pain, auriculotherapy reduced pain intensity (SMD for acute pain, 1.35 [95% CI: 0.08, 2.64], 2 studies; SMD for chronic pain, 1.84 [95% CI: 0.60, 3.07], 5 studies). Removal of poor quality studies did not alter the conclusions. Significant heterogeneity existed among studies of acute and chronic pain, but not perioperative pain. CONCLUSIONS: Auriculotherapy may be effective for the treatment of a variety of types of pain, especially postoperative pain. However, a more accurate estimate of the effect will require further large, well-designed trials.

Missing data in randomized clinical trials for weight loss: scope of the problem, state of the field, and performance of statistical methods.

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.

What leads Indians to participate in clinical trials? A meta-analysis of qualitative studies.

BACKGROUND: With the globalization of clinical trials, large developing nations have substantially increased their participation in multi-site studies. This participation has raised ethical concerns, among them the fear that local customs, habits and culture are not respected while asking potential participants to take part in study. This knowledge gap is particularly noticeable among Indian subjects, since despite the large number of participants, little is known regarding what factors affect their willingness to participate in clinical trials. METHODS: We conducted a meta-analysis of all studies evaluating the factors and barriers, from the perspective of potential Indian participants, contributing to their participation in clinical trials. We searched both international as well as Indian-specific bibliographic databases, including Pubmed, Cochrane, Openjgate, MedInd, Scirus and Medknow, also performing hand searches and communicating with authors to obtain additional references. We enrolled studies dealing exclusively with the participation of Indians in clinical trials. Data extraction was conducted by three researchers, with disagreement being resolved by consensus. RESULTS: Six qualitative studies and one survey were found evaluating the main themes affecting the participation of Indian subjects. Themes included Personal health benefits, Altruism, Trust in physicians, Source of extra income, Detailed knowledge, Methods for motivating participants as factors favoring, while Mistrust on trial organizations, Concerns about efficacy and safety of trials, Psychological reasons, Trial burden, Loss of confidentiality, Dependency issues, Language as the barriers. CONCLUSION: We identified factors that facilitated and barriers that have negative implications on trial participation decisions in Indian subjects. Due consideration and weightage should be assigned to these factors while planning future trials in India.

There are no whole truths in meta-analyses: all their truths are half truths

In a recent letter, Thomsen & Wernberg (2015) rean-alyzed data compiled for our recent paper (Lyonset al., 2014). In that paper, we examined the effectsof macroalgal blooms and macroalgal mats on sevenimportant measures of community structure and eco-system functioning and explored several ecologicaland methodological factors that might explain someof the variation in the observed effects. Thomsen &Wernberg (2015) re-analyzed two small subsets of the data, focusing on experimental studies examining effects of blooms/mats on invertebrate abundance.Their analyses revealed two interesting patterns.First, they showed that macroalgal blooms reducedthe abundance of communities that Thomsen andWernberg categorized as ‘mainly infauna’, whileincreasing the abundance of communities categorized as ‘mainly epifauna’. Second, they showed that theimpacts of macroalgal blooms on ‘mainly infauna’communities increased with algal density in experiments that included multiple levels of algal density.These findings, as well as the conclusions that Thomsen & Wernberg (2015) draw from them, are largely consistent with our own expectations and interpretations. However, we also feel that some caution is required when interpreting the results of their analyses.

Relationships between biodiversity and the stability of marine ecosystems: comparisons at a European scale using meta-analysis.

The relationship between biodiversity and stability of marine benthic assemblages was investigated using existing data sets (n = 28) covering various spatial (m-km) and temporal (1973-2006) scales in different benthic habitats (emergent rock, rock pools and sedimentary habitats) through meta-analyses. Assemblage stability was estimated by measuring temporal variances of species richness, total abundance (density or % cover) and community species composition and abundance structure (using multivariate analyses). Positive relationships between temporal variability in species number and richness were generally observed at both quadrat (<1 m2) and site (100 m2) scales, while no relationships were observed by multivariate analyses. Positive relationships were also observed at the scale of site between temporal variability in species number and variability in community structure with evenness estimates. This implies that the relationship between species richness or evenness and species richness variability is slightly positive and depends on the scale of observation, suggesting that biodiversity per se is important for the stability of ecosystems. Changes within community assemblages in terms of structure are, however, generally independent of biodiversity, suggesting no effect of diversity, but the potential impact of individual species, and/or environmental factors. Except for sedimentary and rock pool habitats, no relationship was observed between temporal variation of the aggregated variable of total abundances and diversity at either scale. Overall our results emphasise that relationships depend on scale of measurements, type of habitats and the marine systems (North Atlantic and Mediterranean) considered.

Effect of interleukin-6 polymorphisms on human longevity: A systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozgyous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I(2)=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I(2)=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis

Background: Habitual consumption of diets with a high glycemic index (GI) and a high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the insulin-like growth factor axis.
Objective: The objective was to conduct a systematic review to assess the association between GI, GL, and risk of digestive tract cancers.
Design: Medline and Embase were searched for relevant publications from inception to July 2008. When possible, adjusted results from a comparison of cancer risk of the highest compared with the lowest category of GI and GL intake were combined by using random-effects meta-analyses.
Results: Cohort and case-control studies that examined the risk between GI or GL intake and colorectal cancer (n = 12) and adenomas (n = 2), pancreatic cancer (n = 6), gastric cancer (n = 2), and squamous-cell esophageal carcinoma (n = 1) were retrieved. Most case-control studies observed positive associations between GI and GL intake and these cancers. However, pooled cohort study results showed no associations between colorectal cancer risk and GI intake [relative risk (RR): 1.04; 95% CI: 0.92, 1.12; n = 7 studies] or GL intake (RR: 1.06; 95% CI: 0.95, 1.17; n = 8 studies). Furthermore, no significant associations were observed in meta-analyses of cohort study results of colorectal cancer subsites and GI and GL intake. Similarly, no significant associations emerged between pancreatic cancer risk and GI intake (RR: 0.99; 95% CI: 0.83, 1.19; n = 5 studies) or GL intake (RR: 1.01; 95% CI: 0.86, 1.19; n = 6 studies) in combined cohort studies.
Conclusions: The findings from our meta-analyses indicate that GI and GL intakes are not associated with risk of colorectal or pancreatic cancers. There were insufficient data available regarding other digestive tract cancers to make any conclusions about GI or GL intake and risk.

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

Aims/hypothesis Glomerular hyperfiltration is a well established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.

Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement
of GFR and presence or absence of hyperfiltration.

Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum
of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20–6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency=48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min-1 1.73 m-2 (95% CI 5.0–22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01).

Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism, and Risk of Retnal Vein Occlusion: A Meta-analysis

Objective: To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease.

Design: Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. Participants and/or Controls: RVO patients and controls.

Methods: Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods.

Main Outcome Measures: tHcy concentrations and MTHFR genotype.

Results: There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 mol/L (95% confidence
interval [CI], 1.8 –3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P0.001, I2 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84–1.71), but again marked heterogeneity (P 0.004, I2 53%) was observed.

Conclusions: There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).

Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes: A meta-analysis of observational studies

Aims/hypothesis: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders.
Methods: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies.
Results: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p<0.001). There was little evidence of heterogeneity between studies (p=0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p=0.01).
Conclusions/interpretation: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Cochrane systematic review and meta-analysis.

Objective To investigate the effects of weaning protocols on the total duration of mechanical ventilation, mortality, adverse events, quality of life, weaning duration, and length of stay in the intensive care unit and hospital.

Design Systematic review.

Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, LILACS, ISI Web of Science, ISI Conference Proceedings, Cambridge Scientific Abstracts, and reference lists of articles. We did not apply language restrictions.

Review methods We included randomised and quasi-randomised controlled trials of weaning from mechanical ventilation with and without protocols in critically ill adults.

Data selection Three authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information.

Results Eleven trials that included 1971 patients met the inclusion criteria. Compared with usual care, the geometric mean duration of mechanical ventilation in the weaning protocol group was reduced by 25% (95% confidence interval 9% to 39%, P=0.006; 10 trials); the duration of weaning was reduced by 78% (31% to 93%, P=0.009; six trials); and stay in the intensive care unit length by 10% (2% to 19%, P=0.02; eight trials). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2)=76%, P

Conclusion There is evidence of a reduction in the duration of mechanical ventilation, weaning, and stay in the intensive care unit when standardised weaning protocols are used, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Some studies suggest that organisational context could influence outcomes, but this could not be evaluated as it was outside the scope of this review.