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"Schoen, Robert"
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Fertility quantum and tempo with cubic age-specific birth rates
To demonstrate the analytical value of a cubic parameterization of the age curve of fertility and to explore its features, especially its usefulness in separating fertility level and fertility timing. Using mathematical analysis, the cubic fertility curve is derived and examined in both continuous and discrete forms. The cubic curve for replacement level fertility is found and expressed in terms of the mean age of fertility. That baseline cubic birth rate density, proportionately adjusted for the level of fertility, is shown to plausibly fit observed birth rates and imply a new approximation for their implicit stable growth rate. Because the proposed cubic model separates the effects of fertility level (quantum) and fertility timing (tempo), it leads to new period/cohort and population momentum relationships and provides a structure for relating fertility trajectories to birth sequences in changing rate models.
Journal Article
Analyzing hyperstable population models
OBJECTIVE Few methods are available for analyzing populations with changing rates. Here hyperstable models are presented and substantially extended to facilitate such analyses. METHODS Hyperstable models, where a known birth trajectory yields a consistent set of age-specific birth rates, are set out in both discrete and continuous form. Mathematical analysis is used to find new relationships between model functions for a range of birth trajectories. RESULTS Hyperstable population projection matrices can create bridges that project any given initial population to any given ending population. New, explicit relationships are found between period and cohort births for exponential, polynomial, and sinusoidal birth trajectories. In quadratic and cubic models, the number of cohort births equals the number of period births a generation later, with a modest adjustment. In sinusoidal models, cohort births equal the number of period births a generation later, modified by a factor related to cycle length. CONTRIBUTION Because of their adaptability, structure, and internal relationships, hyperstable birth models afford a valuable platform for analyzing populations with changing fertility. The new relationships found provide insight into dynamic models and period-cohort connections and offer useful applications to analysts.
Journal Article
Recognizing duration effects in multistate population models
The risk of many demographic events varies by both current state and duration in that state. However, the use of such semi-Markov models has been substantially constrained by data limitations. Here, a new specification of the semi-Markov transition probability matrix in terms of the underlying rates is provided, and a general procedure is developed to estimate semi-Markov probabilities and rates from adjacent population data.
Multistate models recognizing marriage and divorce by duration in state are constructed for United States Females, 1995. The results show that recognizing duration in the married and divorced states adds significantly to the model’s analytical value. Extending the constant-α method to semi-Markov models, 2000–2005 U.S. population data and 1995 cross-product ratios are employed to estimate 2000–2005 duration-dependent transfer probabilities and rates.
The present analyses provide new relationships between probabilities and rates in semi-Markov models. Extending the constant cross-product ratio estimation approach opens new sources of data and expands the range of data susceptible to state-duration analyses.
Journal Article
Circulating Myeloid Derived Suppressor Cells (MDSC) That Accumulate in Premalignancy Share Phenotypic and Functional Characteristics With MDSC in Cancer
Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that accumulate in circulation of cancer patients and at tumor sites where they suppress anti-tumor immunity. We previously reported that in a colon cancer prevention trial of a MUC1 vaccine tested in individuals at increased risk for colon cancer, those who did not mount immune response to the vaccine had higher pre-vaccination levels of circulating MDSC compared to those who did. We also reported that individuals with pancreatic premalignancy, Intraductal Papillary Mucinous Neoplasm (IPMN), had increased circulating levels of MDSC that inversely correlated with spontaneous antibody responses against the pancreatic tumor associated antigen MUC1, abnormally expressed on IPMN. Accumulation of MDSC in cancer and their immunosuppressive role had been well established but their presence in premalignancy was unexpected. In this study we compared MDSC in premalignancy with those in cancer with the hypothesis that there might be differences in the composition of various MDSC subpopulations and their immunosuppressive functions due to different lengths of exposure to disease and/or different tissue microenvironments. In cohorts of patients with premalignant polyps, colon cancer, premalignant IPMN, and pancreatic cancer, we confirmed higher levels of MDSC in premalignancy compared to healthy controls, higher levels of MDSC in cancer compared to premalignancy, but no difference in their subpopulation composition or immunosuppressive capacity. We show that levels of MDSC in premalignancy correlate negatively
with spontaneous MUC1-specific antibody responses and
with polyclonal T cell proliferation and IFN-γ secretion.
Journal Article
Detection and localization of surgically resectable cancers with a multi-analyte blood test
Many cancers can be cured by surgery and/or systemic therapies when detected before they have metastasized. This clinical reality, coupled with the growing appreciation that cancer's rapid genetic evolution limits its response to drugs, have fueled interest in methodologies for earlier detection of the disease. Cohen et al. developed a noninvasive blood test, called CancerSEEK that can detect eight common human cancer types (see the Perspective by Kalinich and Haber). The test assesses eight circulating protein biomarkers and tumor-specific mutations in circulating DNA. In a study of 1000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity of 69 to 98% (depending on cancer type) and 99% specificity. Science , this issue p. 926 ; see also p. 866 A blood test that combines protein and DNA markers may allow earlier detection of eight common cancer types. Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.
Journal Article