Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility.

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction.

In the clinical application of genomic data analysis and modeling, a number of factors contribute to the performance of disease classification and clinical outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling strategy and its clinical use. Although KNN is simple and clinically appealing, large performance variations were found among experienced data analysis teams in the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end points and controls from breast cancer, neuroblastoma and multiple myeloma, we systematically generated 463,320 KNN models by varying feature ranking method, number of features, distance metric, number of neighbors, vote weighting and decision threshold. We identified factors that contribute to the MAQC-II project performance variation, and validated a KNN data analysis protocol using a newly generated clinical data set with 478 neuroblastoma patients. We interpreted the biological and practical significance of the derived KNN models, and compared their performance with existing clinical factors.

Controlled release of α-tocopherol, quercetin, and their cyclodextrin inclusion complexes from linear low-density polyethylene (LLDPE) films into a coconut oil model food system.

Polymer additive migration into a food product is dependent upon numerous factors including the original concentration of the additive in the polymer, its solubility in the food, its diffusion coefficient in the polymer, its partition coefficient between the polymer and food, temperature, and time. The limited solubility of quercetin in linear low-density polyethylene (LLDPE) did not allow release from the film due to phase segregation of the quercetin in the bulk polymer. Increasing the molecular weight of α-tocopherol by ß-cyclodextrin inclusion complexation can greatly reduce its diffusion coefficient in LLDPE. Ziegler-Natta and metallocene LLDPE contain different crystalline structure morphologies and diffusion path networking arrangements that allow for differences in additive release rates. Effective controlled-release packaging should combine ß-cyclodextrin complexation of additives and polymer morphology control to target delivery of an optimal antioxidant concentration to achieve prolonged activity, resulting in extended shelf life foods.

Advances in molecular classification of renal neoplasms.

Kidney neoplasms are classified by light microscopy using the World Health Organization (WHO) system. The WHO system defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. In adults, the common malignant subtypes are variants of renal cell carcinoma (RCC). Histopathologic classification is critical for clinical management of RCC, but is becoming more complex with recognition of novel tumor subtypes, development of procedures yielding small diagnostic biopsies, and emergence of molecular therapies directed at tumor gene activity. Therefore, classification systems based on gene expression are likely to become essential for diagnosis, prognosis and treatment of kidney tumors. Recent DNA microarray studies have shown that clinically relevant renal tumor subtypes are characterized by distinct gene expression profiles, which are useful for discovery of novel diagnostic and prognostic biomarkers. In this review, we summarize the WHO classification system for renal tumors, general applications of microarray technology in cancer research, and specific microarray studies that have advanced knowledge of renal tumor diagnosis, prognosis, therapy and pathobiology.

Beyond single mothers: cohabitation and marriage in the AFDC program.

We investigate the extent and implications of cohabitation and marriage among U.S. welfare recipients. An analysis of four data sets (the Current Population Survey, the National Survey of Families and Households, the Panel Study of Income Dynamics, and the National Longitudinal Survey of Youth) shows significant numbers of cohabitors among recipients of AFDC. An even more surprising finding is the large number of married women on welfare. We also report the results of a telephone survey of state AFDC agencies conducted to determine state rules governing cohabitation and marriage. The survey results indicate that, in a number of respects, AFDC rules encourage cohabitation. Finally, we conduct an analysis of the impact of AFDC rules on cohabitation, marriage, and single motherhood and find weak evidence in support of incentives to cohabit.

Health care coverage for children who are on and off welfare.

Access to adequate health insurance is a key concern of families with children at all income levels. Since 1965, mothers and children on welfare have had health care coverage through the Medicaid program, which has provided a health care safety net for welfare recipients. Although most Americans are insured through their employers, families who leave welfare for employment often find themselves in jobs that do not offer health care coverage, adding to the ranks of the uninsured. This article examines the extent to which poor children and their mothers have private insurance, Medicaid, or no health insurance at all. It documents how recent expansions of Medicaid eligibility to low-income children who do not receive welfare have improved the insurance status of children, though these changes have not helped the mothers who leave welfare for work. Citing evidence that health insurance options influence the welfare and employment decisions of women whose families face health problems, the article suggests that implementing welfare reform at a time when rates of private insurance coverage are declining will be challenging and may expose some families to health risks.

Elevated endothelin-1 levels and persistent stage IV hypertension in a nonvolume overloaded anephric patient.

Persistent hypertension after nephrectomy is in most cases due to increased fluid volume. Endothelin-1 is a potent endogenous vasoconstrictor peptide. Its role in the development and maintenance of hypertension is not completely understood, but it might be significant in some cases. We report a case of stage IV hypertension after nephrectomy with elevated endothelin-1 levels and no volume overload.

Cohort trends in the lifetime distribution of female family headship in the United States, 1968-1985.

We use the PSID Relationship File to estimate cohort trends in the lifetime incidence and duration of female family headship. Hazard (event-history) techniques are used to estimate movements into and out of headship, accounting for duration dependence and left-censored spells. The mean number of years spent in headship between ages 14 and 59 rose dramatically over the period. The increase arose from an increased number of headship spells, including an increase in the number of women ever experiencing headship, but not all from an increase in durations of headship spells; those decreased slightly.

State AFDC rules regarding the treatment of cohabitors: 1993.

This article reports the results of a survey of State Aid to Families with Dependent Children (AFDC) rules regarding the treatment of unrelated cohabitors in households containing AFDC units. We examine State treatment of cash and in-kind contributions by cohabitors and find that the AFDC grant is usually not affected in the cohabitor makes in-kind contributions toward food and shelter expenses of the household. However, the grant generally is reduced if the cohabitor contributes cash to the AFDC unit unless the cash is for shared household expenses. In addition, a few States have specific policies toward cohabitors that are not based on initial evidence of cohabitor contributions.

Medicaid, welfare dependency, and work: is there a causal link?

Medicaid exerts a strong "pull" on potential welfare recipients, increasing the probability that a number of single mothers will apply for and stay on welfare in order to be covered by Medicaid. However, the availability of private health insurance coverage exerts a strong positive influence on women's decisions to work and a strong negative effect on welfare participation rates. If private insurance coverage were as comprehensive as Medicaid and readily available at all jobs, its impact on promoting work would be substantially greater than is the impact of Medicaid in promoting the use of welfare.

The effect of the U.S. welfare system on marital status.

"An issue of long-standing importance in the U.S. welfare system has been its lack of neutrality with respect to family composition, which generally provides payments only to female-headed families--that is, families with no able-bodied male present. Using data from 1969 to 1985 to examine the issue, this study finds that (1) the simple cross-sectional correlations between marital status and welfare benefits are almost always in the expected direction but are generally weak in significance; (2) that the magnitude and significance of the correlations have nevertheless grown over time; and (3) that the correlations for men are no weaker and usually stronger, especially for blacks, than those for women."

Demographic behavior and the welfare state: econometric issues in the identification of the effects of tax and transfer programs.

PIP: It is difficult and risky to identify the effects of tax and transfer programs on demographic behavior. The primary concern of this article is to see if real exogenous variation in these programs' parameters exist to adequately evaluate the effects of the programs on behavior. A 1982 study examined the effect of the Aid to Families with Dependent Children (AFDC), a commonly used example of a US transfer program, on the probability that a female heads a household of children 18 years old with no adult male present. The dependent variable merged household, marital status, and fertility choice into 1 variable. The independent variables included leisure hours and income which also defined a woman's utility function. In this study, the parameters used to represent AFDC effects were not only identified by variation in the AFDC variables. 2 other studies attempting to examine AFDC's effects on demographic behavior (Hutchens [1979] and Ellwood and Bane [1985]) also failed to identify these effects. Ellwood and Bane appropriately concentrated on exogenous program variation (since benefits vary from state to state) and how it might be used in evaluating the effects of AFDC on behavior. They erroneously determined, however, that state variation should not be considered in their model. The studies reviewed in this article looked at AFDC, a program with significant intracountry parameter variation, yet these studies relied on potentially illegitimate sources of variation. Intracountry program variation is less likely to occur in Western Europe and therefore the problem of identifying effects of tax and transfer programs on demographic behavior is apt to be even more severe. Any further such studies should address these issues.^ieng

Optimal life-cycle profiles of fertility and labor supply.

PIP: A model of life cycle fertility is developed using the language and framework of optimal control theory. The chief characteristic of children that distinguishes them from other consumer durables is, in the language of the optimal growth theory, the "irreversibility of investment." As the good does not depreciate in the ordinary sense, the stock must be monotonically nondecreasing over time. The optimal profile of fertility is, for this reason, characterized by the same type of "bang-bang" behavior found in many optimal growth problems. Yet, the fertility decision is complicated considerably by several other factors. Chief among these is the intrinsic relation to the labor-supply decision, for having children implies inevitable constraints on the mother's or father's time. Thus, optimal labor-supply decisions also must be considered. The model is developed in stages, proceeding from very simple to the more complex models. 1 section introduces the impact of fertility on the future demands for home time. It is shown that optimal fertility profiles follow turnpike paths similar to those in the growth-theory literature. A subsequent section introduces labor-supply and human-captial considerations. As the models become more complex, solutions become harder to derive and are often only outlined. The analysis provides some theoretical basis for expecting certain shapes of the life-cycle profiles of fertility, labor supply, and wages. Fertility profiles may be of 2 shapes--one beginning at a high rate, falling to a lower rate, then to zero; and one beginning at zero, rising to a moderate rate, then falling back down to zero. Labor supply profiles can be of a number of different shapes, but the impact of childbearing is to lower hours worked during the early childrearing period. As the children mature, hours worked rise (or at least fall more slowly) as home time responsibilities lessen, although the level to which they rise will probably be lower than before the 1st birth. Log-wage profiles rise during the period before the 1st birth, then either fall or rise more slowly during the early years of childbearing, and then rise again as the children mature. These shapes have been inferred from a control-theory model that is quite complex and which could use considerably more delineation than has been achieved here. Closed-form solutions to the model have not been obtained, nor have any formal comparative dynamics been performed. As the model stands it is too complex to be empirically implemented. Such implementation would be desirable.^ieng

Profiles of fertility, labour supply and wages of married women: a complete life-cycle model.

PIP: Trends in fertility and female labor supply have changed dramatically since World War II. Fertility rates rose steadily from the 1940's until the early 1960's and thereafter declined, while female laborforce participation rates have continually grown since the 1950's. These 2 rates are closely linked. Labor supply and fertility decisions are also life-cycle decisions. In addition, wage and job prospects are related to job choice and in turn to fertility decisions. Labor supply, fertility, and wages are linked in an econometric model which takes into account the problems of heterogeneity of tastes, the problem of missing wage rates through nonworking, and the problem of simultaneous-equations bias. Past works are critiqued, mainly on the basis that few analyses recognize the interrelatedness of fertility and labor supply in any sense--static or dynamic. Nor do most researchers consider age-specific fertility equations in analyzing female labor supply. Moffitt's model is a beginning analysis of fertility and labor supply as a joint consumer-demand choice. Patterns of a couple's future consumption, wife's labor supply, and births are assumed to be planned at the beginning of marriage. These patterns depend on the constraints of budget, fertility, and of inverse production (the differing amounts of time it takes to care for a child as the child matures) as well as wage accumulation. Exogenous wealth and beginning wages are considered as well. This model does not account for a woman's work experience prior to marriage. According to the model, fertility rates rise in the 1st year of marriage and subsequently fall off. Employment rates drop off at an accelerating rate until the 6th year of marriage and then increase. A rise in wage level decreases the probability of birth and increases the probability ow working. Also, changes in fertility rates have more to do with wage changes than with a woman's cohort.^ieng

Rapid direct determination of lead in evaporated milk by anodic stripping voltammetry without sample pretreatment.

The method presented describes the direct determination of lead in evaporated milk in which the milk ashing step prior to analysis is eliminated. Digital instrument readout units are microgram Pb/mL milk. Total analysis time after instrument calibration is less than 3 min per sample. Range of the method is 0.05-1.0 ppm lead in milk, and precision of the method expressed by relative standard deviation of duplicate pairs ranged from 30% at 0.1 micrograms/mL to 3% at 1.0 micrograms/mL of lead in milk. The method compares favorably with the AOAC official first action anodic stripping voltammetric method (25.074). In addition, the method appears to work equally well for skim evaporated milk, sweetened condensed milk, and nonfat powdered dry milk when the latter two are reconstituted with water according to product label instructions. Recovery and interference studies are presented.

Direct determination of lead in evaporated milk and apple juice by anodic stripping voltammetry: collaborative study.

A method for the direct determination of lead in evaporated milk and in fruit juice with no prior sample digestion was successfully collaborated by 13 laboratories. The anodic stripping voltammetric (ASV) method studied consisted of adding 0.2 mL aliquots of evaporated milk or 0.3 mL aliquots of fruit juice to 2.9 mL of a dechelating reagent, Metexchange. The reagent-sample mixture is then analyzed for lead by ASV with no further sample preparation. Each collaborator received 24 samples, 2 each at 5 different levels (0.07-0.70 ppm for spiked evaporated milk and 0.09-0.87 ppm for spiked apple juice) along with duplicate practice samples of labeled lead content at each of 2 levels for each sample type. All unknowns were coded with random numbers. Approximately 69% of the reporting laboratories had never analyzed either evaporated milk or fruit juice for lead. Average time between receipt of samples and reporting of results was 1.6 days for all laboratories. The pooled variations between duplicate determinations for apple juice and evaporated milk were 0.00059 and 0.00043, respectively. The method was adopted official first action for both fruit juice and evaporated milk.