Prognostic role of lemur tyrosine kinase-3 germline polymorphisms in adjuvant gastric cancer in Japan and the United States

Lemur tyrosine kinase-3 (LMTK3) was recently identified as an estrogen receptor (ER)-α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Because different predominant ER distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was carried out to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and 137 U.S. patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival [HR, 4.37; 95% confidence interval (CI), 2.08-9.18; P < 0.0001] and overall survival (OS; HR, 3.69; 95% CI, 1.65-8.24; P = 0.0014) in the Japanese males and time to recurrence (HR, 7.29; 95% CI, 1.07-49.80; P = 0.043) in the U.S. females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR, 3.04; 95% CI, 1.08-8.56; P = 0.035) and the U.S. males (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patients with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.

Escaping the Holocaust: human and health capital of refugees to the United States, 1940-42

The large-scale persecution of Jews during World War II generated massive refugee movements. Using data from 20,441 predominantly Jewish passengers from 19 countries traveling from Lisbon to New York between 1940 and 1942, we analyze the last wave of refugees escaping the Holocaust and verify the validity of height as a proxy for human and health capital. We further show this episode of European migration displays well-known features of migrant self-selection: early migrants were taller than late migrants; a large migrant stock reduces migrant selectivity; and economic barriers to migration
apply. Our findings show that Europe experienced substantial losses in human and health capital while the US benefitted from the immigration of European refugees.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

Causes and prevalence of visual impairment among adults in the United States.

OBJECTIVES: To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. METHODS: Summary prevalence estimates of blindness (both according to the US definition of < or =6/60 [< or =20/200] best-corrected visual acuity in the better-seeing eye and the World Health Organization standard of < 6/120 [< 20/400]) and low vision (< 6/12 [< 20/40] best-corrected vision in the better-seeing eye) were prepared separately for black, Hispanic, and white persons in 5-year age intervals starting at 40 years. The estimated prevalences were based on recent population-based studies in the United States, Australia, and Europe. These estimates were applied to 2000 US Census data, and to projected US population figures for 2020, to estimate the number of Americans with visual impairment. Cause-specific prevalences of blindness and low vision were also estimated for the different racial/ethnic groups. RESULTS: Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. CONCLUSIONS: Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.

Prevalence of cataract and pseudophakia/aphakia among adults in the United States.

OBJECTIVES:

To determine the prevalence of cataract and pseudophakia/aphakia in the United States and to project the expected change in these prevalence figures by 2020.

METHODS:

Summary prevalence estimates of cataract and of pseudophakia/aphakia were prepared separately for black, white, and Hispanic persons (for whom only cataract surgery data were available) in 5-year age intervals starting at 40 years for women and men. The estimates were based on a standardized definition of various types of cataract: cortical, greater than 25% of the lens involved; posterior subcapsular, present according to the grading system used in each study; and nuclear, greater than or equal to the penultimate grade in the system used. Data were collected from major population-based studies in the United States, and, where appropriate, Australia, Barbados, and Western Europe. The age-, gender-, and race/ethnicity-specific rates were applied to 2000 US Census data, and projected population figures for 2020, to obtain overall estimates.

RESULTS:

An estimated 20.5 million (17.2%) Americans older than 40 years have cataract in either eye, and 6.1 million (5.1%) have pseudophakia/aphakia. Women have a significantly (odds ratio = 1.37; 95% confidence interval, 1.26-1.50) higher age-adjusted prevalence of cataract than men in the United States. The total number of persons who have cataract is estimated to rise to 30.1 million by 2020; and for those who are expected to have pseudophakia/aphakia, to 9.5 million.

CONCLUSION:

The number of Americans affected by cataract and undergoing cataract surgery will dramatically increase over the next 20 years as the US population ages.

The prevalence of refractive errors among adults in the United States, Western Europe, and Australia.

OBJECTIVE:

To estimate the prevalence of refractive errors in persons 40 years and older.

METHODS:

Counts of persons with phakic eyes with and without spherical equivalent refractive error in the worse eye of +3 diopters (D) or greater, -1 D or less, and -5 D or less were obtained from population-based eye surveys in strata of gender, race/ethnicity, and 5-year age intervals. Pooled age-, gender-, and race/ethnicity-specific rates for each refractive error were applied to the corresponding stratum-specific US, Western European, and Australian populations (years 2000 and projected 2020).

RESULTS:

Six studies provided data from 29 281 persons. In the US, Western European, and Australian year 2000 populations 40 years or older, the estimated crude prevalence for hyperopia of +3 D or greater was 9.9%, 11.6%, and 5.8%, respectively (11.8 million, 21.6 million, and 0.47 million persons). For myopia of -1 D or less, the estimated crude prevalence was 25.4%, 26.6%, and 16.4% (30.4 million, 49.6 million, and 1.3 million persons), respectively, of whom 4.5%, 4.6%, and 2.8% (5.3 million, 8.5 million, and 0.23 million persons), respectively, had myopia of -5 D or less. Projected prevalence rates in 2020 were similar.

CONCLUSIONS:

Refractive errors affect approximately one third of persons 40 years or older in the United States and Western Europe, and one fifth of Australians in this age group.

Prevalence of open-angle glaucoma among adults in the United States.

OBJECTIVE:

To estimate the prevalence and distribution of open-angle glaucoma (OAG) in the United States by age, race/ethnicity, and gender.

METHODS:

Summary prevalence estimates of OAG were prepared separately for black, Hispanic, and white subjects in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US census data and to projected US population figures for 2020 to estimate the number of the US population with OAG.

RESULTS:

The overall prevalence of OAG in the US population 40 years and older is estimated to be 1.86% (95% confidence interval, 1.75%-1.96%), with 1.57 million white and 398 000 black persons affected. After applying race-, age-, and gender-specific rates to the US population as determined in the 2000 US census, we estimated that OAG affects 2.22 million US citizens. Owing to the rapidly aging population, the number with OAG will increase by 50% to 3.36 million in 2020. Black subjects had almost 3 times the age-adjusted prevalence of glaucoma than white subjects.

CONCLUSIONS:

Open-angle glaucoma affects more than 2 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to more than 3 million by 2020.

Trends in Approval Times for Genetically Engineered Crops in the United States and the European Union

Genetically engineered (GE) crops are subject to regulatory oversight to ensure their safety for humans and the environment. Their approval in the European Union (EU) starts with an application in a given Member State followed by a scientific step (risk assessment), and ends with a political decision-making step (risk management); and in the United States (US) it starts with a scientific (field trial) step and ends with a ‘bureaucratic’ decision-making step. We investigated trends for the time taken for these steps and the overall time taken for approving GE crops in the US and the EU (traders in these commodities). Results show that from 1996-2015 the overall time trend for approval in the EU decreased and then flattened off, with an overall mean completion-time of 1,763 days. In the US in 1998 there was a break in the trend of the overall approval time: Initially, from 1988 until 1997 the trend decreased with a mean approval time of 1,321 days; from 1998-2015, the trend almost stagnated with a mean approval time of 2,467 days.