STATISTICAL METHODS TO ANALYZE CONTINUOUS RISK VARIABLES IN INDIVIDUAL PATIENT DATA META-ANALYSES: APPLICATION ON A STUDY ON TOBACCO SMOKING AND GASTRIC CANCER RISK IN A CONSORTIUM OF CASE-CONTROL STUDIES (THE STOMACH POOLING (STOP) PROJECT)

Gastric cancer represents the fifth most common cancer and the third leading cause of cancer death over both sexes worldwide, with almost 1 million cases and over 700 000 deaths estimated in 2012. The presence of Helicobacter Pylori is a key determinant of gastric cancer. However, other factors, including familial, genetic, environmental and social characteristics appear to also have a role in the etiology of this disease. Tobacco smoking has been associated with increased risk of morbidity and mortality from many diseases and for gastric cancer. Various epidemiologic consortia have been established on several cancers but not yet on gastric cancer. A pooled-analysis of worldwide case-control studies may allow to investigate indebt gastric cancer etiology. Particularly, this large dataset will allow us to better investigate life style characteristics including tobacco smoking, in relation to gastric cancer. The Stomach cancer Pooling (StoP) Project is an international epidemiological consortium. The inclusion criteria for study participation are: a case-control study design (including nested case-control analyses derived from cohort study) and an inclusion of at least 80 cases of gastric cancer (including both cardia and non-cardia location). The aim of my project is to conduct a pooled analysis on data from already available international studies, on the role of tobacco smoking in the etiology of gastric cancer in particular, the number of cigarettes per day and the duration of smoking, using adequate statistical approaches. During the first year of the PhD program, my project was focused on the two-stage analysis. This method is used to analyze meta-analysis and could be applicable in a case of pooled case-control analysis. The first step of the method consists in calculate adjusted study-specific odds ratios (OR) in order to overcome differences across studies in terms of design or population. The second step consists in summarize these study-specific risks using meta-analytic methods which take into account the heterogeneity across studies. During my second year of PhD program, I studied various statistical methods regarding the analysis of non-linear continuous variables. In addition to transform continuous variables in category, I considered more flexible approaches including fractional polynomials. During my third year of PhD program, I focused my research on a way to adapt these latest methods to the analysis of pooled case-control studies. In particular I chose to use factional polynomials in a two-stage method due to their simple interpretation and also because their estimates can be easily pooled through a two-stage analysis. The first step analysis is to perform a fractional polynomial for each study. For each value of the power term (or couple of power terms for the second-order fractional polynomials), the second stage of the model is performed. The pooled dose-response relationship is estimated according to a bivariate random-effects model. The estimate of the trend components could be obtained using restricted maximum likelihood (REML) or maximum likelihood (ML) estimation. The second-stage model is fitted to the data considering each combination of the power terms. The best model, denoted by the optimal power combination is defined as the one minimizing the deviance or the Akaike Information Criterion (AIC), a penalized likelihood which takes into account the number of parameter. We analyzed data on 21 studies including 10,040 cases and 25,602 controls. To investigate the relationship between tobacco smoking and gastric cancer risk, we first used a classical method, building categories of smokers 1) in terms of quantity; \u201cnever smokers\u201d, \u201c20 cigarettes per day\u201d and 2) in terms of smoking duration; \u201cnever smokers\u201d, \u201c30 years of smoking\u201d. We analyzed these variable with a two-stage method. This risk significantly increase with the number of cigarettes per day to reach an OR of 1.29 (95% CI 1.06-1.57 )for smokers of more than 20 cigarettes and, with duration to reach an OR of 1.32 (95% CI 1.17-1.49) for smokers smoking for more than 30 years compared to never smokers. These effects of increasing risk are confirmed by different statistical models of analysis including linear model and fractional polynomials, considering the number of cigarettes per day and the duration as a continuous variable. Results from our analysis confirm that there is an association between cigarette smoking and gastric cancer risk. This risk increases with the number of cigarettes and the duration of smoking. These effects of increasing risk are confirmed by different statistical models of analysis including linear models and fractional polynomials, considering the number of cigarettes per day and the duration as continuous variables. To our knowledge this is the first study using fractional polynomials through a two-stage random effect methods for pooled case-control studies. Through this method we were able to take into account study-specific adjustment variables and heterogeneity across studies thanks to mixed effect modeling. Categorization has the advantage of a simple epidemiologic interpretation and presentation result. However it assumes that the relationship between the risk of disease and the exposure is flat within intervals and also that there is a discontinuity in response when a category cutpoint is crossed, which is unlikely realistic. Considering exposure variables may avoid these limitations. The relationship between cigarette smoking and gastric cancer risk may be discerned from the categorical analysis, but the analysis of the variable in continuous through polynomials brought additional information in particular to understand the possible threshold and possible changes in slopes

The Salmonella Genomic Island 1 Is Specifically Mobilized In Trans by the IncA/C Multidrug Resistance Plasmid Family

BACKGROUND: The Salmonella genomic island 1 (SGI1) is a Salmonella enterica-derived integrative mobilizable element (IME) containing various complex multiple resistance integrons identified in several S. enterica serovars and in Proteus mirabilis. Previous studies have shown that SGI1 transfers horizontally by in trans mobilization in the presence of the IncA/C conjugative helper plasmid pR55. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the ability of different prevalent multidrug resistance (MDR) plasmids including extended-spectrum β-lactamase (ESBL) gene-carrying plasmids to mobilize the multidrug resistance genomic island SGI1. Through conjugation experiments, none of the 24 conjugative plasmids tested of the IncFI, FII, HI2, I1, L/M, N, P incompatibility groups were able to mobilize SGI1 at a detectable level (transfer frequency <10(-9)). In our collection, ESBL gene-carrying plasmids were mainly from the IncHI2 and I1 groups and thus were unable to mobilize SGI1. However, the horizontal transfer of SGI1 was shown to be specifically mediated by conjugative helper plasmids of the broad-host-range IncA/C incompatibility group. Several conjugative IncA/C MDR plasmids as well as the sequenced IncA/C reference plasmid pRA1 of 143,963 bp were shown to mobilize in trans SGI1 from a S. enterica donor to the Escherichia coli recipient strain. Depending on the IncA/C plasmid used, the conjugative transfer of SGI1 occurred at frequencies ranging from 10(-3) to 10(-6) transconjugants per donor. Of particular concern, some large IncA/C MDR plasmids carrying the extended-spectrum cephalosporinase bla(CMY-2) gene were shown to mobilize in trans SGI1. CONCLUSIONS/SIGNIFICANCE: The ability of the IncA/C MDR plasmid family to mobilize SGI1 could contribute to its spread by horizontal transfer among enteric pathogens. Moreover, the increasing prevalence of IncA/C plasmids in MDR S. enterica isolates worldwide has potential implications for the epidemic success of the antibiotic resistance genomic island SGI1 and its close derivatives

Maize genetics Committee on Outreach, Diversity, Inclusion, and Education (CODIE) 2020-2021 update.

Virtual meeting

Public awareness of the link between alcohol and cancer in England in 2015: A population-based survey

Background: Public knowledge of the association between alcohol and cancer is reported to be low. We aimed to provide up-to-date evidence for England regarding awareness of the link between alcohol and different cancers and to determine whether awareness differs by demographic characteristics, alcohol use, and geographic region. Methods: A representative sample of 2100 adults completed an online survey in July 2015. Respondents were asked to identify which health outcomes, including specific cancers, may be caused by alcohol consumption. Logistic regressions explored whether demographic, alcohol use, and geographic characteristics predicted correctly identifying alcohol-related cancer risk. Results: Unprompted, 12.9% of respondents identified cancer as a potential health outcome of alcohol consumption. This rose to 47% when prompted (compared to 95% for liver disease and 73% for heart disease). Knowledge of the link between alcohol and specific cancers varied between 18% (breast) and 80% (liver). Respondents identified the following cancers as alcohol-related where no such evidence exists: bladder (54%), brain (32%), ovarian (17%). Significant predictors of awareness of the link between alcohol and cancer were being female, more highly educated, and living in North-East England. Conclusion: There is generally low awareness of the relationship between alcohol consumption and cancer, particularly breast cancer. Greater awareness of the relationship between alcohol and breast cancer in NorthEast England, where a mass media campaign highlighted this relationship, suggests that population awareness can be influenced by social marketing

Dietary glycemic load and gastric cancer risk in Italy

We investigated gastric cancer risk in relation to dietary glycemic index (GI) and glycemic load (GL), which represent indirect measures of carbohydrate absorption and consequently of dietary insulin demand, in a case-control study conducted in northern Italy between 1997 and 2007, including 230 patients with the incident, histologically confirmed gastric cancer and 547 frequency matched controls, admitted to the same hospitals as cases with acute non-neoplastic conditions. We used conditional logistic regression models, including terms for major recognised gastric cancer risk factors and non-carbohydrate energy intake. The odds ratios (ORs) in the highest vs lowest quintile were 1.9 (95% CI: 1.0–3.3) for GI and 2.5 (95% CI: 1.3–4.9) for GL. Compared with participants reporting low GL and high fruits/vegetables intake, the OR rose across strata of high GL and low fruits/vegetables, to reach 5.0 (95% CI: 2.2–11.5) for those reporting low fruits/vegetables intake and high GL. Our study may help to explain the direct relation observed in several studies between starchy foods and gastric cancer risk

Effect of population structure corrections on the results of association mapping tests in complex maize diversity panels

Association mapping of sequence polymorphisms underlying the phenotypic variability of quantitative agronomical traits is now a widely used method in plant genetics. However, due to the common presence of a complex genetic structure within the plant diversity panels, spurious associations are expected to be highly frequent. Several methods have thus been suggested to control for panel structure. They mainly rely on ad hoc criteria for selecting the number of ancestral groups; which is often not evident for the complex panels that are commonly used in maize. It was thus necessary to evaluate the effect of the selected structure models on the association mapping results. A real maize data set (342 maize inbred lines and 12,000 SNPs) was used for this study. The panel structure was estimated using both Bayesian and dimensional reduction methods, considering an increasing number of ancestral groups. Effect on association tests depends in particular on the number of ancestral groups and on the trait analyzed. The results also show that using a high number of ancestral groups leads to an over-corrected model in which all causal loci vanish. Finally the results of all models tested were combined in a meta-analysis approach. In this way, robust associations were highlighted for each analyzed trait

Do Worry and Brooding Predict Health Behaviors? A Daily Diary Investigation

Background Meta-analyses have reported associations between perseverative cognition (both worry and brooding) and increased engagement in health-risk behaviors, poorer sleep, and poorer physiological health outcomes. Method Using a daily diary design, this study investigated the within- and between-person relationships between state and trait perseverative cognition and health behaviors (eating behavior, physical activity, alcohol consumption, and sleep) both crosssectionally and prospectively. Participants (n = 273, 93% students, Mage = 20.2, SD = 4.11, 93% female) completed morning and evening diaries across 7 consecutive days. Results Multilevel modeling analyses revealed that, cross-sectionally, higher levels of state worry were associated with more time spent sitting and higher levels of state brooding predicted less daily walking. Conclusion Worry and brooding may represent useful intervention targets for improving inactivity and walking levels, respectively

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Mediterranean diet and colorectal cancer risk : A pooled analysis of three Italian case-control studies

Background: Adherence to the Mediterranean diet (MD) is associated with a reduced risk of several cancers. However, studies conducted in Mediterranean regions are scanty. Methods: To investigate the relation between MD and colorectal cancer risk in Italy, we pooled data from three case-control studies, including a total of 3745 colorectal cancer cases and 6804 hospital controls. Adherence to the MD was assessed using an a priori Mediterranean Diet Score (MDS), based on nine components. Results: Compared with the lowest adherence to the MD (0-2 MDS), the odds ratio (OR) was 0.52 (95% confidence interval (CI) 0.43-0.62) for the highest adherence (7-9 MDS), with a significant inverse trend in risk (P<0.0001). The OR for a 1-point increment in the MDS was 0.89 (95% CI 0.86-0.91). The inverse association was consistent across studies, cancer anatomical subsites and strata of selected covariates. Conclusions: This Italian study confirms a favourable role of MD on colorectal cancer risk