Background Endoscopic screening has been proposed for patients with symptoms of gastro-oesophageal reflux disease (GERD) in the hope of reducing mortality from oesophageal adenocarcinoma. Assessing the net benefits of such a strategy requires a precise understanding of the cancer risk in the screened population. Aim To estimate precisely the association between symptoms of GERD and oesophageal adenocarcinoma. Methods Systematic review and meta-analysis of population-based studies with strict ascertainment of exposure and outcomes. Results Five eligible studies were identified. At least weekly symptoms of GERD increased the odds of oesophageal adenocarcinoma fivefold (odds ratio = 4.92; 95% confidence interval = 3.90, 6.22), and daily symptoms increased the odds sevenfold (random effects summary odds ratio = 7.40, 95% confidence interval = 4.94, 11.1), each compared with individuals without symptoms or less frequent symptoms. Duration of symptoms was also associated with oesophageal adenocarcinoma, but with very heterogeneous results, and unclear thresholds. Conclusions Frequent GERD symptoms are strongly associated with oesophageal adenocarcinoma. These results should be useful in developing epidemiological models of the development of oesophageal adenocarcinoma, and in models of interventions aimed at reducing mortality from this cancer.

OBJECTIVES Esophageal adenocarcinoma (EAC) is a devastating disease that has risen in incidence over the past several decades. Barrett's esophagus (BE) is an associated premalignant lesion. Current preventative efforts rely on endoscopic screening of individuals with gastroesophageal reflux disease (GERD) symptoms and surveillance endoscopy for those with BE. However, some recent studies have found a high prevalence of BE in patients without GERD, and others have found little or no association with GERD. We hypothesized that studies of higher-quality design show weaker associations of GERD with BE, and that GERD is only weakly associated with short-segment Barrett's esophagus (SSBE). METHODS We performed a systematic literature search in multiple online electronic databases regardless of language. Eligible studies required visualization of columnar mucosa and histological confirmation of intestinal metaplasia, and GERD symptoms ascertained by questionnaire or interview. The highest-quality sampling design was defined a priori by both cases and controls identified among unselected research volunteers (“research design”) rather than by patients selected for endoscopy for clinical indications (“clinical design”), which introduces selection and ascertainment bias. A priori, heterogeneity was defined by Cochrane's Q P < 0.20 and the inconsistency index (I2; 25% low, 50% moderate, and 75% high). Heterogeneity of results can reflect significant differences in study design or effect modification by strata of outcomes. RESULTS Systematic review identified 13,392 citations. Evaluation identified 108 potentially relevant journal articles, of which 26 met eligibility. Of these, 14 studies identified cases of BE and controls based on clinical indication (“clinical design”), and 6 used the “research design.” The remaining six studies identified cases of BE from patients undergoing endoscopy for clinical indication and controls among patients without known BE (“cases clinical/controls research”). The summary odds ratio (OR) for the association of GERD with BE from all studies was 2.90 (95% confidence interval (CI), 1.86–4.54), but the results were very heterogeneous (P = 0.0001; I2 = 89%). When stratified by BE length and sampling design, the studies with clinical design showed substantial, but heterogeneous, associations with SSBE (OR, 2.38; 95% CI, 1.21–4.70; P = 0.02; I2 = 62%), and stronger and homogeneous association with long-segment BE (LSBE; fixed effects OR, 2.96; 95% CI, 1.69–5.19; P = 0.25; I2 = 25%). In the research study design, stratifying by length of BE resolved the heterogeneity and showed a strong association between GERD and LSBE (fixed effects OR, 4.92; 95% CI, 2.01–12.0; P = 0.30; I2 = 19%) and no association with SSBE (fixed effects OR, 1.15; 95% CI, 0.763–1.73; P = 0.84; I2 = 0%). Funnel plots showed potential evidence for bias against dissemination of small negative studies. CONCLUSIONS In the highest-quality studies, GERD symptoms are not associated with SSBE, but increased the odds of LSBE by f...

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With many degraded environments undergoing restoration efforts, there is a growing need for the optimization of direct seeding practices. Seeds planted on wildlands are often consumed by rodents, leading to reduced plant establishment. Coating seeds in rodent aversive products may prevent seed‐predation. We tested 10 seed‐coating formulations containing products expected to deter rodents, namely: ghost and cayenne pepper powders; essential oils from bergamot, neem, and pine; methyl‐nonyl‐ketone, anthraquinone, activated carbon, beta‐cyclodextrin, and a blank coating containing no rodent deterrents to serve as a control treatment. Each treatment was applied to Pseudoroegneria spicata (bluebunch wheatgrass) seeds. These seeds germinated similarly to uncoated control seeds unless the coating contained methyl‐nonyl‐ketone which reduced germination. When seeds were offered to Ord's kangaroo rats (Dipodomys ordii), they strongly avoided the treatments in favor of uncoated control seeds. Notably, the blank coating, lacking active ingredients, still elicited 99% avoidance. However, these results indicated behavior when alternative food sources are readily available, a scenario rare in nature. To address this, a second feeding experiment was conducted to observe D. ordii's behavior under calorie‐restricted conditions. D. ordii were subjected to a fast period, then offered only one treatment. Under these conditions, many subjects chose to consume coated seeds, but to a lesser degree than subjects offered control seeds. Seeds coated in ghost pepper, neem oil, and activated carbon reduced consumption by 47–50%. Given these lab results, we would expect these treatments to increase native plant establishment following the direct seeding of wildlands by protecting seeds from rodent predation.