Patterns of lung cancer mortality in 23 countries: Application of the Age-Period-Cohort model

BACKGROUND: Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. METHODS: International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer. RESULTS: The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. CONCLUSION: Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of carrot (daucus carota) microstructure on carotene bioaccessibility in the upper gastrointestinal tract. 2: In vivo digestions

Nutrient bioaccessibility and subsequent absorption will be directly influenced by changes in food structure during gastrointestinal processing. The accompanying paper (Tydeman et al. J. Agric. Food Chem. 2010, 58, doi: 10.1021/jf101034a) reported results on the effect of carrot processing on the release of carotene into lipid phases during in vitro gastric and small intestinal digestions. This paper describes results from in vivo digestion of two of the types of processed carrot used previously, raw grated carrot and cooked carrot mashed to a pure. Ileostomy effluents from human volunteers fed meals containing the carrot material were used to study tissue microstructure and carotene release. Raw carrot shreds and intact cells that had survived the pureing process were identifiable in ileal effluent. The gross tissue structure in the shreds had not changed following digestion. Carotene-containing particles remained encapsulated in intact cells, but were absent from ruptured cells. Microscopy revealed marked changes to the cell walls including swelling and pectin solubilization, which increased in severity with increasing residence time in the upper gut. These observations were entirely consistent with the in vitro observations. It was concluded that a single intact cell wall is sufficient to reduce carotene bioaccessibility from a cell by acting as a physical barrier, which is not broken down during upper gut digestion

Soluble non-starch polysaccharides derived from complex food matrices do not increase average lipid droplet size during gastric lipid emulsification in rats

The creation of a finely dispersed lipid emulsion is essential for efficient hydrolysis of dietary triglycerides. The effectiveness of emulsification within the stomach depends upon the shear force generated by gastric motility and the concentration of emulsifiers present in the gastric contents. Other dietary constituents can modify these factors, and previous studies have suggested that the presence of soluble non-starch polysaccharides (NSP) during digestion might increase the average size of intraluminal emulsion droplets. In the present study, we developed a new technique for the isolation and analysis of intraluminal lipid emulsions by optical diffraction analysis. The method was applied to rats fed powdered semipurified diets that were free of all NSP or supplemented with insoluble cellulose, guar gum, or NSP derived from apple, carrot or rolled oats. Cellulose had no significant effect on emulsion size, and there was no evidence that the average sizes of lipid droplets in the gastric fundus or antrum were higher than control values in rats fed diets supplemented with any source of soluble NSP. In the groups fed oats and cooked carrot NSP, the mean droplet diameters approached half the values for diets free of NSP or containing insoluble cellulose. The difference between rats fed NSP from cooked carrot and those fed cellulose was significant in the proximal stomach (P < 0.05), and that between rats fed raw oats and rats fed cellulose was significant in the distal stomach (P < 0.05). Soluble dietary fiber does not inhibit lipid or cholesterol absorption via any inhibition of lipid emulsification