Tumorigenesis begins long before the growth of a clinically detectable lesion and, indeed, even before any of the usual morphological correlates of pre-malignancy are recognizable. Field ...cancerization, which is the replacement of the normal cell population by a cancer-primed cell population that may show no morphological change, is now recognized to underlie the development of many types of cancer, including the common carcinomas of the lung, colon, skin, prostate and bladder. Field cancerization is the consequence of the evolution of somatic cells in the body that results in cells that carry some but not all phenotypes required for malignancy. Here, we review the evidence of field cancerization across organs and examine the biological mechanisms that drive the evolutionary process that results in field creation. We discuss the clinical implications, principally, how measurements of the cancerized field could improve cancer risk prediction in patients with pre-malignant disease.
An appreciation of colonic crypt organization has become essential to any understanding of tumorigenesis in the colon. Intestinal crypts house tissue-specific, multipotential stem cells, which are ...located in the niche at the base of the intestinal crypt and are capable of regenerating all intestinal cell types. Recent advances in our understanding of crypt biology, including how mutations in stem cells become fixed and expand within the epithelium, has led to new theories on the origins of colonic adenomas and cancers.
Designing an effective framework for financing higher education is a key objective of policymakers in developed and developing countries. While we have a good understanding of how college financing ...options affect students' college outcomes in developed countries, less is known about the impact of these programs in developing countries. In this paper, I employ several quasi-experimental designs and novel administrative data from Jamaica to estimate the effect of need-based grants and student loan funding on students' academic achievement and labor market outcomes. The results indicate that the students who benefited from either program had a higher GPA, graduated at higher rates, and were more likely to remain in college beyond their second year. While both programs induce treated students to reduce their engagement in the labor market during college, I find that each program had an opposing impact on students’ earnings in the early years after their expected graduation date.
•Loan and grant funding improve the academic outcomes of low-income students.•Both loan and grant funding induce students to reduce their labor market engagement during college.•Grant funding improves the post-college labor market outcomes of some treated students.•Student loan recipients are more likely to accept job offers that pay them below their productive capacity.
•The conventional approaches of evaluating traffic laws produce unreliable results.•The contiguous-counties design yields robust estimates of various traffic laws.•DUI penalties that restrict future ...vehicle use reduce traffic fatalities.•Open container and zero-tolerance laws reduce alcohol-induced fatal crashes.
In the United States, about 28 lives are lost daily in motor vehicle accidents that involve an alcohol-impaired driver. While most states have enacted various traffic laws to address this phenomenon, little consensus exists on the causal impact of these laws in reducing alcohol-induced fatalities. This paper exploits quasi-random variation in state-level laws to estimate the causal effect of alcohol-related traffic laws on the frequency of fatal accidents. This is identified from the discontinuities in traffic laws among contiguous counties that are separated by a shared state border. We present robust evidence that the conventional approaches that are typically utilized in the literature may erroneously estimate the effectiveness of several alcohol-related laws.
Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by ...quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+). Furthermore, we show that, in adenomatous crypts (APC−/−), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.
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•Somatic mtDNA mutations for quantitative lineage tracing in human intestine•Human intestinal stem cells evolve according to a neutral drift process•Loss of APC causes an increase in the stem cell loss/replacement rate•Intestinal crypts divide once every 30–40 years in the normal human colon
Baker et al. examine the in vivo stem cell biology of human colonic crypts. They reveal that each crypt contains a small number of functional stem cells and that stem cell division is predominantly symmetric and also quantify perturbation of stem cell architecture within adenomas. Additionally, they measure the division rate of human colonic crypts as once every 30–40 years in the healthy colon and demonstrate that the crypt division rate is increased 10-fold within small adenomas.
•I find that the Dean’s list and academic probation policies improve students’ GPAs.•Both policies induced treated students to strategically choose easier courses.•The probation policy caused treated ...students to adjust their program of study.•The results are not sensitive to the strictness of the academic probation policy.•I find no adverse long-term impact of being affected by either programs.
This paper examines how college initiatives that ascribe public recognition or written reprimand to a set standard of academic performance impact students’ decision-making. Many colleges utilize programs such as the Dean’s list and academic probation policies as mediums to encourage student success. These policies impose a cost on affected students through the potential loss of acquired benefits or the threat of expulsion for failing to perform above the established standard in future semesters. Using the regression discontinuity design, I find that students who are named to the Dean’s list or put on academic probation during their first year improved their subsequent academic performance. To achieve this improvement, students on the Dean’s list are induced into selecting courses and instructors that are more likely to result in higher letter grades and those bounded by the academic probation policy are likely to switch majors and employ a maximin strategy for expected grades when choosing courses.
Students form beliefs about their expected performance based on incomplete information about the past distribution of grades. This may lead students to sub-optimally choose their level of effort and ...ultimately harm their actual academic performance. Using a field experiment, this paper examines the impact of randomly exposing students to accurate instructor-level information about the past distribution of grades in an introductory economics course. We find that while the intervention had a small positive impact on students’ average test scores, it improved the likelihood of passing the course by 10 percentage points. In addition, the results indicate that moderate-achievers, females, and students from higher-income households are most likely to benefit from treatment. The intervention also favored the students who had high expectations about their performance in the course and those with stronger priors about the expected grade distribution.
In this study, we argue that the basic clonal unit that makes up the Barrett’s segment is at the level of the gland. There is expansion of this clonal unit, the gland, by fission, and there is ...evidence that the Barrett’s segment is itself a clonal proliferation. Barrett’s esophagus arises from both goblet cell-containing metaplasia and non-goblet cell-containing metaplasia and may arise from a stable clone, but the genomic changes occurring are subject to selection, usually with little or no evolution, appearing indolent from the evolutionary perspective. Genomic changes leading to dysplastic phenotypes are selected, but without any single clone predominating within the segment.
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