Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

The Age Structure of Occupations and Jobs

Age segmentation in the labor force can be analyzed in terms of the age distributions of occupations. In this paper we show that the majority of detailed census occupations conform to one of five basic age profiles. Further, these age profiles have meaning as they derive from the operation of well-defined institutional forces. We discuss the relevance of industry for a refined understanding of occupational-age patterns and conclude with some observations about the likely consequence of a change in the age of compulsory retirement for the age distributions of different occupations

Prospectus, October 26, 1983

LEARNING LAB IS A LIFE SAVER; News Digest; What to do about childhood stress; Braille room fills needs of the blind; PC Happenings; Did you know that?; How to reorganize homemaking chores; TV results; Pumpkin Contest; Health Information; C.A.A.R.; WPCD quizzes high schools; Register for spring semester; Apples remain fave fruit; Be cool in case of fire; Rural Illinois growth increases; Cowboy Brock programs sports; Pulitzer winner visits C-U; Quality circles solve problems; Oktoberfest is today; Around Parkland; The truth behind Halloween is haunting; Brighten a Soldier\u27s Christmas; Interesting story ideas brighten series; Passion at Krannert; Zelig restores Allen\u27s stature; Classified; Krannert adds on; Fast Freddy statistics; Fast Freddy Contest; Bowling scoreshttps://spark.parkland.edu/prospectus_1983/1007/thumbnail.jp

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial ({"type":"clinical-trial","attrs":{"text":"NCT00769704","term_id":"NCT00769704"}}NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease

Dynamic system-optimal traffic assignment using a state space model

We propose a new mathematical formulation for the problem of optimal traffic assignment in dynamic networks with multiple origins and destinations. This problem is motivated by route guidance issues that arise in an Intelligent Vehicle-Highway Systems (IVHS) environment. We assume that the network is subject to known time-varying demands for travel between its origins and destinations during a given time horizon. The objective is to assign the vehicles to links over time so as to minimize the total travel time experienced by all the vehicles using the network. We model the traffic network over the time horizon as a discrete-time dynamical system. The system state at each time instant is defined in a way that, without loss of optimality, avoids complete microscopic detail by grouping vehicles into platoons irrespective of origin node and time of entry to network. Moreover, the formulation contains no explicit path enumeration. The state transition function can model link travel times by either impedance functions, link outflow functions, or by a combination of both. Two versions (with different boundary conditions) of the problem of optimal traffic assignment are studied in the context of this model. These optimization problems are optimal control problems for nonlinear discrete-time dynamical systems, and thus they are amenable to algorithmic solutions based on dynamic programming. The computational challenges associated with the exact solution of these problems are discussed and some heuristics are proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30420/1/0000041.pd

Pharmacokinetics and safety of elotuzumab combined with lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: Results of a phase Ib study

AbstractIntroductionThe present study evaluated the pharmacokinetics and safety of elotuzumab, a humanized IgG1 monoclonal antibody against signaling lymphocyte activation molecule-F7, combined with lenalidomide and dexamethasone, in patients with multiple myeloma (MM) and renal impairment.Patients and MethodsPatients with MM and normal renal function (NRF) (creatinine clearance [CrCl] ≥ 90 mL/min), severe renal impairment (SRI) (CrCl < 30 mL/min, not requiring dialysis), or end-stage renal disease (ESRD) (requiring dialysis) were enrolled in this open-label, phase Ib study. Elotuzumab (10 mg/kg), lenalidomide (5-25 mg), and dexamethasone (40 mg) were administered in 28-day cycles until disease progression or unacceptable toxicity developed. The primary endpoint was single-dose elotuzumab pharmacokinetics.ResultsA total of 26 patients (median age, 63 years) were treated (NRF, n = 8; SRI, n = 9; ESRD, n = 9). The median baseline CrCl was 105 mL/min (range, 84-146 mL/min) for those with NRF and 26 mL/min (range, 15-33 mL/min) for those with SRI. Twenty-three patients (89%) had received previous therapy (median, 2 regimens; range, 1-7). Treatment was discontinued in 6 patients with NRF, 4 with SRI, and 5 with ESRD, primarily because of disease progression. The mean elotuzumab serum concentrations were comparable across groups (n = 23). No statistically significant differences were observed in the maximum observed serum concentration, area under the concentration–time curve from time 0 to the last quantifiable serum concentration, or area under the concentration–time curve from time 0 to infinity when the SRI and ESRD groups were compared with the NRF group (P > .05). All patients had ≥ 1 adverse event (AE). Of the 8 patients with NRF, 9 with SRI, and 9 with ESRD, 7, 8, and 7 experienced grade 3 to 4 AEs. The overall response rates were 75% in the NRF, 67% in the SRI, and 56% in the ESRD groups.ConclusionThe results of the present study support the use of elotuzumab for the treatment of patients with MM and renal dysfunction without dose adjustment

High permeability explains the vulnerability of the carbon store in drained tropical peatlands

Tropical peatlands are an important global carbon (C) store but are threatened by drainage for palm oil and wood pulp production. The store's stability depends on the dynamics of the peatland water table, which in turn depend on peat permeability. We found that an example of the most abundant type of tropical peatland—ombrotrophic domes—has an unexpectedly high permeability similar to that of gravel. Using computer simulations of a natural peat dome (NPD) and a ditch-drained peat dome (DPD) we explored how such high permeability affects water tables and peat decay. High permeability has little effect on NPD water tables because of low hydraulic gradients from the center to the margin of the peatland. In contrast, DPD water tables are consistently deep, leaving the upper meter of peat exposed to rapid decay. Our results reveal why ditch drainage precipitates a rapid destabilization of the tropical peatland C store

The epithelial origin of a stromal cell population in adenocarcinoma of the rat prostate.

Dunning R3327-H rat prostate adenocarcinoma cells, when grown in syngeneic (Copenhagen) rats or nude mice, produce tumors with prominent hypercellular stroma. The authors have previously demonstrated the presence of anomalous steroid-sensitive cells in both the epithelium and stromal compartments of this model system. In order to better understand the histogenesis of these cells, the authors studied samples of the tumor which were radiolabeled overnight with tritiated dihydrotestosterone (3H-DHT). Frozen sections of the tissues were thaw-mounted onto autoradiographic emulsion-coated slides to permit silver grain identification in association with nuclei of androgensensitive cells. Surprisingly, numerous silver grains were found to be associated with nuclei of large cells within the stroma. Therefore, these cells were termed "epithelioid" pending confirmation of their origin. To further define these cells and their relationship to the surrounding matrix, autoradiograms have now been examined immunohistochemically with antibodies directed against the basement membrane glycoprotein, laminin, as well as antibodies specific for intermediate cytoskeletal filaments. Following identification of acinar basement membranes, epithelioid cells were identifiable both in the stroma and in the acinar epithelial cell layer. Histochemical staining with acid phosphatase, a marker for prostatic epithelium, was performed and shown to be present in acinar epithelial cells as well as in epithelioid cells. Additionally, fluorescence-activated cell sorting was employed to characterize the DNA content of cell types within the H tumor. Epithelioid cells were found to be in highest concentration in an aneuploid peak with a ploidy of approximately 6N. The autoradiographic, immunohistochemical, cytometric, and ultramicroscopic studies suggest that 1) epithelioid cells are epithelial derived stromal cells; 2) these epithelioid cells arise by pathologic division of aneuploid neoplastic precursor cells of approximately 3N ploidy, which are found within the prostatic epithelium; and 3) the resulting 6N cells degrade the basement membrane locally, invade the stroma, and populate it. Here, they can be distinguished from fibroblasts by their size, acid phosphatase activity, and hormone receptor content. Thus, the term "epithelioid" is inappropriate; and these cells should be regarded simply as large neoplastic epithelial (LNE) cells. The presence of this cell type suggests that this tumor subline represents a useful naturally occurring model for the study of the initial stages of neoplastic transformation