Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program

Background:

There has been growing interest in the overdiagnosis of breast cancer as a result of mammography screening. We report incidence rates in British Columbia before and after the initiation of population screening and provide estimates of overdiagnosis.

Methods:

We obtained the numbers of breast cancer diagnoses from the BC Cancer Registry and screening histories from the Screening Mammography Program of BC for women aged 30–89 years between 1970 and 2009. We calculated age-specific rates of invasive breast cancer and ductal carcinoma in situ. We compared these rates by age, calendar period and screening participation. We obtained 2 estimates of overdiagnosis from cumulative cancer rates among women between the ages of 40 and 89 years: the first estimate compared participants with nonparticipants; the second estimate compared observed and predicted population rates.

Results:

We calculated participation-based estimates of overdiagnosis to be 5.4% for invasive disease alone and 17.3% when ductal carcinoma in situ was included. The corresponding population-based estimates were −0.7% and 6.7%. Participants had higher rates of invasive cancer and ductal carcinoma in situ than nonparticipants but lower rates after screening stopped. Population incidence rates for invasive cancer increased after 1980; by 2009, they had returned to levels similar to those of the 1970s among women under 60 years of age but remained elevated among women 60–79 years old. Rates of ductal carcinoma in situ increased in all age groups.

Interpretation:

The extent of overdiagnosis of invasive cancer in our study population was modest and primarily occurred among women over the age of 60 years. However, overdiagnosis of ductal carcinoma in situ was elevated for all age groups. The estimation of overdiagnosis from observational data is complex and subject to many influences. The use of mammography screening in older women has an increased risk of overdiagnosis, which should be considered in screening decisions.There is growing interest in the overdiagnosis of breast cancer resulting from mammography screening.^1,2 It has been suggested that incidence rates after the introduction of mammography screening are higher than would be expected from the early detection of clinically significant disease alone. The clinical importance of ductal carcinoma in situ has long been unclear, and recent attention has also focused on the potential overdiagnosis of invasive cancer.^1,3,4 Furthermore, more frequent screening, wider age ranges and higher false-positive rates in much of North America may result in increased overdiagnosis⁵ in comparison with Europe, the source of most reports.The Screening Mammography Program of BC provides bilateral 2-view mammography screening to female residents of British Columbia. The program began in 1988 at a single location and progressively expanded by adding centres in larger communities and extending mobile services; by 2000, geographic coverage was effectively 100%. Women aged 40–79 years are eligible to self-refer. Since 1997, women aged 40–49 years are reminded to return annually, and those over 50 years of age are reminded to return biennially. Women outside of this age-range can undergo screening with a physician’s referral. Rates of abnormal results on screening mammography in British Columbia are comparable to the community rates seen in the United States.⁶Our primary objective for this study was to estimate the extent of overdiagnosis of breast cancer due to screening. To do this, we examined cancer rates in the following subpopulations: all women 1970–1979, and women in 2005–2009 classified by active and nonactive participation in screening. From 1970 to 1979, screening was infrequent and no organized program existed. In the period 2005–2009, screening was well established and the use of hormone replacement therapy for menopause had declined.⁷ Our secondary objective was to determine the changes in population incidence of breast cancer, both invasive and ductal carcinoma in situ, following the implementation of a population-based screening program. Thus, we report an analysis of population age-specific incidence rates in British Columbia over a 40-year period (1970–2009).     

The crystal structure of methenyltetrahydromethanopterin cyclohydrolase from Methanobrevibacter ruminantium

Methenyltetrahydromethanopterin cyclohydrolase (Mch) is involved in the methanogenesis pathway of archaea as a C₁ unit carrier where N⁵‐formyl‐tetrahydromethanopterin is converted to methenyl‐tetrahydromethanopterin. Mch from Methanobrevibacter ruminantium was cloned, purified, crystallized and its crystal structure solved at 1.37 Å resolution. A biologically active trimer, the enzyme is composed of two domains including an N‐terminal domain of six α‐helices encompassing a series of four β‐sheets and a predominantly anti‐parallel β–sheet at the C‐terminus flanked on one side by α‐helices. Sequence and structural alignments have helped identify residues involved in substrate binding and trimer formation. Proteins 2013; 81:2064–2070. © 2013 Wiley Periodicals, Inc.     

A large archosauriform tooth with multiple supernumerary carinae from the Upper Triassic of New Mexico (USA), with comments on carina development and anomalies in the Archosauria

Here we report a tooth of a large archosauriform from the Upper Triassic of New Mexico, USA that displays developmental anomalies of carina formation. This tooth has two supernumerary carinae, both on the lingual side of the tooth. Previously, carina anomalies of this sort were primarily known from theropod dinosaurs, but always from the labial surface. Integrating this specimen into a reassessment of the published accounts of carina anomalies in other fossil diapsids reveals that supernumerary carinae are more widespread throughout Archosauriformes than previously reported. Our interpretation of this developmental anomaly highlights the present lack of understanding of tooth development in archosaurs, particularly carina formation, and suggests that crown morphology development in archosauriforms may be constrained differently than it is in mammals. This developmental constraint may explain the differences observed between the complexity found in mammal and archosauriform cusp morphology.     

Stories from Below: Subject-generated Comics

This article discusses the efficacy of grassroots comics as a practical and affordable method of realizing localized subject-generated development communication goals that focus explicitly on the interests and capacities of the subject community. The Khwe San, living in Platfontein in South Africa's Northern Cape Province, constitute the subject community. The study is informed by contemporary shifts in development theory, particularly that of participatory communication, which values individuals who live in a community as active participants in the research process. The use of grassroots comics is based on theoretical concepts in current literature regarding the field of development communication that are critical of older, top-down theories of development. My analysis and findings are presented in terms of possible implications that they might have for broader discussions regarding contemporary development theory or visual methodologies with respect to participatory communication practices.     

Liposomal Delivery Systems for Encapsulation of Ferrous Sulfate: Preparation and Characterization

Liposomal delivery systems for water-soluble bioactives were prepared using the pro-liposome and the microfluidization technologies. Iron, an essential micronutrient as ferrous sulfate and ascorbic acid, as an antioxidant for iron were encapsulated in the liposomes. Liposomes prepared by the microfluidization technology using 6% (w/w) concentration of the lipid encapsulated with ferrous sulfate and ascorbic acid had particle size distributions around 150 to 200 nm, whereas liposomes from the pro-liposome technology resulted in particle sizes of about 5 μm. The encapsulation efficiency of ferrous sulfate was 58% for the liposomes prepared by the microfluidization using 6% (w/w) lipid and 7.5% of ferrous sulfate concentrations, and it was 11% for the liposomes from pro-liposome technology using 1.5% (w/v) lipid and 15% of ferrous-sulfate concentration. Both the liposomes exhibited similar levels of oxidative stability, demonstrating the feasibility of microfluidization-based liposomal delivery systems for large-scale food/nutraceutical applications.     

Interactions of Quinoxaline Antibiotic and DNA.: The Molecular Structure of a Triostin A—d(GCGTACGC) Complex

Abstract

The crystal structure of a DNA. octamer d(GCGTA.CGC) complexed to an antitumor antibiotic, triostin A, has been solved and refined to 2.2 Å resolution by x-ray diffraction analysis. The antibiotic molecule acts as a true bis intercalator surrouding the d(CpG) sequence at either end of the unwound right-handed DNA. double helix. A.s previously observed in the structure of triostin A.—d(CGTA.CG) complex (A.H.-J. Wang, et. al., Science, 225,1115–1121 (1984)), the alanine amino acid residues of the drug molecule form sequence-specific hydrogen bonds to guanines in the minor groove. The two central A · T base pairs are in Hoogsteen configuration with adenine in the syn conformation. In addition, the two terminal G · C base pairs flanking the quinoxaline rings are also held together by Hoogsteen base pairing. This is the first observation in an oligonucleotide of. Hoogsteen G · C base pairs where the cytosine is protonated. The principal functional components of a bis-intercalative compound are discussed.     

Production and Mass Transfer Characteristics of Non-Newtonian Biopolymers for Biomedical Applications

ABSTRACT:?

The market for microbial biopolymers is currently expanding to include several emerging biomedical applications. Specifically, these applications are drug delivery and wound healing. A fundamental understanding of the key fermentation parameters is necessary in order to optimize the production of these biopolymers. Considering that most microbial biopolymer systems exhibit non-Newtonian rheology, oxygen mass transfer can be an important parameter to optimize and control. In this article, we present a critical review of recent advances in rheological and mass transfer characteristics of selected biopolymers of commercial interest in biomedical applications.