Evaluation of the reproductive and developmental risks of caffeine

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 μg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the "caffeine teratogenic syndrome." Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses.     

Chromatin and heritability: how epigenetic studies can complement genetic approaches

Despite the success in using genome-wide association studies to identify many loci associated with human disease, there are several gaps in understanding of how common genetic diseases are manifested. Epigenetic studies, which focus on DNA and chromatin modifications, have the potential to complement genetic approaches and provide more insight into mechanism, environmental effects and modes of inheritance, including the potential for non-DNA-based heritability. However, there are considerable challenges in designing and interpreting epigenetic studies associated with disease. Here, I review recent studies focused on individual variation in chromatin, and outline how epigenome-based studies can be used to complement genetic studies. In particular, I see more benefit to epigenetic studies being performed in the context of genetic studies, rather than as separate investigations.     

Association between Tooth Loss and Gastric Cancer: A Meta-Analysis of Observational Studies

Observational studies showed that tooth loss is associated with gastric cancer, but the findings are inconsistent. In this study, a meta-analysis was conducted to evaluate the relationship between tooth loss and gastric cancer. Relevant studies were screened in PubMed and Embase databases, and nine observational studies were considered eligible for the analysis. The combined relative risks for the highest versus the lowest categories of tooth loss were 1.86 (95% CI: 1.08–3.21) and 1.31 (95% CI: 1.12–1.53) in case control and cohort studies, respectively. However, unstable results were observed in the stratified and sensitivity analysis. The current evidence, based solely on four case-control studies and five cohort studies, suggested that tooth loss is a potential marker of gastric cancer. However, we can not concluded at this time that tooth loss may be a risk factor for gastric cancer due to significant heterogeneity among studies and mixed results between case-control studies and cohort studies. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of gastric cancer.     

Transcultural aspects of eating disorders: A critical literature review

A review of studies addressing anorexia nervosa and bulimia nervosa among Native Americans, African-Americans, Hispanics, Asians, Africans, and Middle Easterners yielded only 35 studies, of which 22 were qualitative case reports, three were clinical quantitative studies, and ten were non-clinical quantitative studies. The case studies reported symptoms similar to those of Caucasian patients, and eating disorders were reported in all SES classes. The clinical studies, all reported from Asian countries, described a number of cases for eating disorders quite different from one another. The non-clinical quantitative studies reported a number of cases consistent with the ranges previously reported for controlled samples of non-clinical Caucasian populations. We found few or no quantitative studies on eating disorders from Hispanic, Middle Eastern, African, or Asian countries other than Japan.     

造礁石珊瑚群落结构研究的概况,问题和前景

造礁石珊瑚作为珊瑚礁生态系统中的关键生物类群,其群落结构是珊瑚礁系统研究中的一个重 要方面。本文回顾了20余年以来世界各国对造礁石珊瑚群落结构研究所取得的主要进展和认识,指出了目前研究中存在的问题并分析了不同空间范围研究结论之间的缺乏一致性和中等干扰假说的不足。 最后,结合珊瑚礁生态系统基础理论和应用发展的需求,本文探讨了造礁石珊瑚群落结构研究的前景。     

Amphibian Temperature Regulation Studies in the Field and Laboratory

Studies on thermoregulation in the laboratory and field havecome a long way from the early work done between 1940 and 1960.While some physiological studies on amphibians have progressedat the same rate as those on reptiles, field studies have beenfar behind. Laboratory studies have largely delt with thermalacclimation, evaporative water loss, and thermal and moisturegradient behavior. Field studies, following early summariesof body temperatures of field animals, have stressed behavioralthermoregulation; yet, detailed studies on behavioral thermoregulationin amphibians have been completed for only a handful of species.A few studies have placed behavioral and physiological thermoregulationinto an ecological or energetic framework; these studies arereviewed, and suggestions are made for future work.     

Meta‐analysis results are unlikely to be biased by differences in variance and replication between ecological lab and field studies

A recurrent question in meta‐analyses is the validity of including both field and laboratory studies in a single analysis, given the differences in characteristics such as the duration or size of these experiments. In particular, are field studies consistently more variable, longer in duration, or do they differ from laboratory studies in other important ways? We examined these questions using an unusually large and comprehensive data set on grazing effects on benthic microalgae, consisting of 865 experiments including both field and lab studies and using marine, lotic or lentic communities of small benthic primary producers. We found there was greater variation in field than laboratory studies, but that this difference explained only 0.5% of the variance in the coefficient of variation. Field studies were longer, on average, than laboratory studies, but experiments in the two systems did not differ consistently in other ecological or design parameters. Thus, the common assumption that field studies have higher variances than laboratory studies, while true, explained only a tiny proportion of the heterogeneity in variation. Therefore, perhaps surprisingly, any conclusions from research syntheses would be unlikely to be affected by consistent differences in variance (or other parameters we examined) between the laboratory and field studies.     

What risks should be permissible in controlled human infection model studies?

Controlled human infection model (CHIM) studies involve the intentional exposure of healthy research volunteers to infectious agents. These studies contribute to knowledge about the cause or development of disease and to the advancement of vaccine research. But they also raise ethical questions about the kinds of risks that should be permissible and whether limits should be imposed on research risks in CHIM studies. Two possible risk thresholds have been considered for CHIM studies. The first suggests constraining ethically permissible risks according to a minimal risk threshold and the second endorses a higher risk threshold that excludes irreversible or fatal infections. I argue that neither of these thresholds is persuasive and situate questions about risk thresholds in CHIM studies within a broader debate about permissible risks in research. I argue that risks in CHIM studies should be constrained according to limits on research risks that do not offer corresponding benefits in all studies rather than developing a unique risk threshold for CHIM studies. I then propose five recommendations for the ethical assessment of risk in CHIM studies.     

Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case-Control and Cohort Studies

Background

Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta-analysis of published case-control and cohort studies to quantify the association.

Methods

Potentially eligible studies were found on PubMed and EMBASE databases through May 31, 2015. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity.

Results

Our final analyses included 20 observational studies comprising nearly 5 thousand cases of pancreatic cancer. When comparing the highest with the lowest categories of vitamin C intake, the summary odds ratio/relative risk for case-control studies (14 studies), cohort studies (6 studies) and all studies combined was 0.58 (95% CI: 0.52–0.66), 0.93 (95% CI: 0.78–1.11) and 0.66 (95% CI: 0.58–0.75), respectively. The difference in the findings between case-control and cohort studies was statistically significant (P < .001). Possible publication bias was shown in the meta-analysis of case-control studies.

Conclusion

There is insufficient evidence to conclude any relationship between vitamin C intake and risk of pancreatic cancer. The strong inverse association observed in case-control studies may be affected by biases (eg, recall and selection biases) that particularly affect case-control studies and/or potential publication bias. Future prospective studies of vitamin C intake and pancreatic cancer are needed.     

The association between smokeless tobacco use and pancreatic adenocarcinoma: A systematic review

BackgroundSmokeless tobacco is a possible risk factor for developing pancreatic adenocarcinoma. This systematic review addressed the question: Is there an association between smokeless tobacco use and pancreatic adenocarcinoma diagnosis?MethodsFive electronic databases, grey literature, and citations of relevant articles were searched to identify studies. Six researchers double-reviewed records for inclusion in the review. The information extracted from these studies was selected using criteria outlined in the Newcastle–Ottawa Quality Assessment Scale for observational studies. A qualitative synthesis of included studies was performed.ResultsThe search of electronic databases resulted in a total of 1747 citations. Eleven studies met the inclusion criteria for this review, including three cohort studies, seven case control studies and one study that pooled data from multiple case-control studies. Studies were heterogeneous in their assessment of exposure intensity and ascertainment of outcomes. Quality of the studies varied. Existing investigations of the association of interest appear to exhibit several types of biases including selection bias, information bias and bias in the analysis.ConclusionThe association between smokeless tobacco use and pancreatic adenocarcinoma is inconclusive. More definitive conclusions regarding this relationship await the results of more methodologically rigorous epidemiologic studies.     

Extrapolating non-target risk of Bt crops from laboratory to field

The tiered approach to assessing ecological risk of insect-resistant transgenic crops assumes that lower tier laboratory studies, which expose surrogate non-target organisms to high doses of insecticidal proteins, can detect harmful effects that might be manifested in the field. To test this assumption, we performed meta-analyses comparing results for non-target invertebrates exposed to Bacillus thuringiensis (Bt) Cry proteins in laboratory studies with results derived from independent field studies examining effects on the abundance of non-target invertebrates. For Lepidopteran-active Cry proteins, laboratory studies correctly predicted the reduced field abundance of non-target Lepidoptera. However, laboratory studies incorporating tri-trophic interactions of Bt plants, herbivores and parasitoids were better correlated with the decreased field abundance of parasitoids than were direct-exposure assays. For predators, laboratory tri-trophic studies predicted reduced abundances that were not realized in field studies and thus overestimated ecological risk. Exposure to Coleopteran-active Cry proteins did not significantly reduce the laboratory survival or field abundance of any functional group examined. Our findings support the assumption that laboratory studies of transgenic insecticidal crops show effects that are either consistent with, or more conservative than, those found in field studies, with the important caveat that laboratory studies should explore all ecologically relevant routes of exposure.     

Methodology of assessment and reporting of safety in anti-malarial treatment efficacy studies of uncomplicated falciparum malaria in pregnancy: a systematic literature review

Background

Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy.

Methods

Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808).

Results

Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/48) followed participants through to pregnancy outcome. Fetal loss was assessed in 34 studies (89%, 34/38), but the definition of miscarriage and stillbirth were defined only in 11 (32%, 11/34) and 7 (21%, 7/34) studies, respectively. Preterm birth was assessed in 26 studies (68%, 26/38) but was defined in 16 studies (62%, 16/26). Newborn weight was assessed in 30 studies (79%, 30/38) and length in 10 studies (26%, 10/38). Assessment of birth weight took gestational age into account in four studies (13%, 4/30). Congenital abnormalities were reported in 32 studies (84%, 32/38). Other common risk factors for adverse pregnancy outcomes were not well-reported.

Conclusion

Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies. A standard list of minimal necessary parameters to assess and report the safety component of efficacy studies of anti-malarials in pregnancy is proposed.

     

Integrative factor analysis — An unsupervised method for quantifying cross-study consistency of gene expression data

Integrative analyses of multiple gene expression studies are frequently performed. In the setting of two studies, integrative correlation (IGC) can be used to assess the consistency of co-expression of a given gene. For three or more studies, an extension of IGC gives a global score per gene. We propose to extend IGC and use factor analysis to assess the study-specific consistency of co-expression of genes when there are three or more studies, possibly on different platforms. Our method is able to identify studies whose expression patterns are different from others. Filtering genes based on our score is shown to improve the concordance of association with phenotype across studies.     

Smoking and Risk of Erectile Dysfunction: Systematic Review of Observational Studies with Meta-Analysis

Background

There are many recent observational studies on smoking and risk of erectile dysfunction (ED) and whether smoking increases the risk of ED is still inconclusive. The objective of this meta-analysis was to synthesize evidence from studies that evaluated the association between smoking and the risk of ED.

Methods

We searched PubMed, Embase, Web of Science, and Scopus in January 2013 to identify cohort and case-control studies that evaluated the association between smoking and ED. Study quality of included studies was assessed by the Newcastle-Ottawa scale. Random-effects meta-analyses were used to combine the results of included studies.

Results

Four prospective cohort studies and four case-control studies involving 28, 586 participants were included. Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Compared with non-smokers, the overall odd ratio of ED in prospective cohort studies was 1.51(95% CI: 1.34 to 1.71) for current smokers, and it was 1.29 (95% CI: 1.07 to 1.47) for former smokers. Evidence of publication bias was not found.

Conclusion

Evidence from epidemiological studies suggests that smoking, especially current smoking, may significantly increase the risk of ED     

Some fundamental aspects of epidemiology: a guide for laboratory scientists.

Epidemiologic methods used to study human diseases are often unfamiliar to the laboratory scientist. This paper outlines the standard method by which epidemiologic studies are classified, explains the methodologic strengths and weaknesses of different kinds of studies, and notes the kinds of inferences that can be drawn from each. Surveys on populations are treated first, followed by sample surveys. Prospective (follow-up) studies, in which groups of subjects are followed in time, are a basic epidemiologic method. Alternatives to these studies that do not require similar time commitments but may allow similar inferences are record studies. Retrospective, or case-control studies, are often the only feasible method for studying rare diseases. However, diseases with long latency periods and problems in control selection can make these studies difficult to analyze and interpret.     

Dendroclimatology in Kazakhstan

We have reviewed 43 studies related to dendroclimatology in Kazakhstan, and additionally 13 studies related to other subfields of dendrochronology, which have been published during the past 40 years. This review also includes studies published in Russian, Kazakh, German and Chinese languages, which are not easily accessible to international researchers.Dendroclimatic studies in Kazakhstan began back in the days of the Soviet Union and were actively conducted in the southern and northern parts of the country. With the collapse of the Soviet Union dendroclimatic studies stopped and resumed only 15-20 years later. Within the last 5 years, the intensity and quality of dendroclimatic studies increased significantly. Several research groups have investigated climate-growth relationships of Scots pine, Silver birch, Siberian larch, Siever’s apple and Schrenk spruce. Schrenk spruce was the most widely studied of these species, and several climatic reconstructions have been published based off their climate-growth relationships. Results of most studies on Schrenk spruce demonstrated good consistency, allowing the general patterns of climate-growth relationships to be accurately traced. Unfortunately, studies on other tree species have either lower level or represented just by one or two studies. It would therefore be premature to make any generalizations on these species at the current stage.We conclude that there is a good potential and good base for continuing dendroclimatic studies in Kazakhstan. There is a need to close several research gaps which limit our knowledge, such as chronologies’ length, application of new methods, species composition and spatial coverage. Closing these gaps let us significantly improve the dendrochronological network of Kazakhstan and provide important data for further hydrological and climate studies in Kazakhstan.     

Gene polymorphisms and chronic obstructive pulmonary disease

The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large‐sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.