Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

A phase II evaluation of esorubicin in ovarian cancer. A Southwest Oncology Group study.

Patients with a pathologically confirmed diagnosis of metastatic or advanced epithelial-type ovarian carcinoma were entered into a Phase II trial of esorubicin. Eligibility criteria included measurable disease; performance status (SWOG) 0-2; no more than one prior chemotherapeutic regimen; and no prior doxorubicin therapy. The starting esorubicin dosing schedule was 30 mg/m2 every 3 weeks for good risk patients and 25 mg/m2 every 3 weeks for poor risk patients. Twenty-one patients were eligible for evaluation of response and toxicity to treatment. These patients received a median of 3 courses of esorubicin (range 1-13 courses). None of the 21 patients experienced a response to esorubicin. Median survival was 5.5 months. Leukopenia was the major toxicity. Eleven (79%) of the good risk patients and 2 (29%) of the poor risk patients experienced severe to life-threatening leukopenia. Mild to severe anemia was seen in 10 (71%) of the good risk patients and 7 (100%) of the poor risk patients. We conclude that esorubicin is ineffective in the treatment of ovarian cancer patients who have received primary chemotherapy.

Late complications of the Estes operation for tubal infertility. A case report.

The Estes procedure was designed to restore fertility in women with infertility related to tubal factors by transposition of an ovary into the uterine cavity with preservation of its vascular pedicle. This procedure was performed most commonly in the middle of this century in the United States. Many of these women are now perimenopausal and therefore entering the age of risk for ovarian neoplasia. We treated a patient who developed large intramyometrial cystic masses more than 20 years after undergoing an Estes procedure.

Ovarian fetiform teratoma (homunculus) in a 9-year-old girl.

An infarcted ovarian mass, removed from a 9-year-old girl, was composed of a thin-walled cyst containing a fetiform structure. At its cranial pole was a ruptured cyst lined by skin and a diaphanous fibrous membrane associated with long, darkly pigmented hair. The remainder of the fetiform structure was covered by skin bearing fine lanugo hair. Rudimentary upper limb buds were present. At the caudal pole were two extremities that included feet, toes, and nails. Radiographic studies demonstrated portions of skull, vertebral, and limb bones. Microscopical examination revealed primitive brain tissue at the base of the cephalic cavity and a spinal cord along the entire length of the trunk with ganglia and peripheral nerves extending outward from it. Notochordal tissue was associated with one vertebral body. A mucus-filled endodermal tube containing glandular outgrowths also ran the length of the trunk. This patient is one of the youngest reported with an ovarian homunculus or fetiform teratoma. This specimen is among the very few recorded cases in the literature and reflects the highest degree of organized development exhibited by a single germ cell undergoing neoplasia.

Wide excision (nonnerve sparing) radical retropubic prostatectomy using an initial perirectal dissection.

PURPOSE: Positive surgical margin rates after radical retropubic prostatectomy are reported to range from 25 to 50% in contemporary series. We report on 53 nonnerve sparing radical retropubic prostatectomies performed with attention paid to extending the margin of attached periprostatic tissue. This was accomplished primarily by initial perirectal release of periprostatic tissues at the level of longitudinal rectal fibers posterior and lateral to the prostate. This perirectal release ensures that maximal quantities of periprostatic tissue will remain with the prostate specimen and will not be attenuated or sheared away at subsequent stages of the procedure. MATERIALS AND METHODS: Pathological material was examined for capsular penetration and surgical margins using transverse whole mount sections of the prostate at 4 to 5 mm. intervals. Patients were followed at regular intervals with physical examinations and serum prostate specific antigen (PSA) determinations. RESULTS: The series consisted of 6, 5, 14 and 28 cases of clinical stages T1b, T1c, T2a and T2b cancer, respectively. Mean PSA was 10.0 ng./ml. and mean Gleason score was 5.9. Capsular penetration was observed in 47 of 53 cases (89%) and positive surgical margins were noted in 7 (13%). With a median followup of 3.61 years 2 patients experienced PSA defined recurrence. CONCLUSIONS: We believe that positive surgical margin rates may be decreased when technical modifications are directed at increasing the amount of periprostatic tissue excised with the surgical specimen.

Placental-site trophoblastic tumor (trophoblastic pseudotumor): case report demonstrating failure of chemotherapy, surgery, and radiotherapy to control metastatic disease.

A case of metastatic placental-site trophoblastic tumor (trophoblastic pseudotumor) is presented and compared to four previously reported cases. Chemotherapy with MAC (methotrexate, dactinomycin, cyclophosphamide), aggressive surgical debulking, and radiotherapy were ineffective in producing disease regression. Only two of the four similar cases in the literature showed short responses (4-7 months) to several different aggressive multiagent chemotherapy regimens. Optimal therapeutic outcome is likely to result from an early diagnosis and aggressive surgical treatment of localized tumor.

Isolated calcaneal metastasis in a patient with endometrial adenocarcinoma.

A 55-year-old woman with a history of Stage IA endometrial adenocarcinoma, previously treated with surgery and intracavitary radiation therapy, had an isolated calcaneal metastasis. Normal radiographs led to a delay in the diagnosis of her relapse. An ankle computed tomographic scan finally identified a mass, and the surgical biopsy specimen confirmed the diagnosis. This is the first reported case of an isolated calcaneal metastasis in endometrial adenocarcinoma to the authors' knowledge.

bcl-2 is down-regulated in atypical endometrial hyperplasia and adenocarcinoma.

The bcl-2 protein, which protects cells from apoptosis, is normally expressed in a number of adult tissues. Dysregulated bcl-2 expression, secondary to (14;18) chromosomal translocation, seems to promote the development of follicular lymphomas, and recent findings of bcl-2 protein in several solid tumors suggest that it might contribute to the genesis of many other neoplasms. bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory endometrium, which suggests that its expression is estrogen regulated. Because the development of most endometrial carcinomas is associated with hyperestrogenic states, we began the investigation of the role of bcl-2 in endometrial carcinogenesis by immunohistochemically quantifying its expression in proliferative, hyperplastic, atypically hyperplastic, and carcinomatous endometrium. The results of this study show that bcl-2 is relatively highly expressed in proliferative (n = 11) and hyperplastic (n = 18) endometrium, with respective mean staining scores of 3.59 and 3.47 (scale, 0-4), but is significantly (P < 0.001) down-regulated in atypical hyperplasia (n = 11; score, 0.82), and adenocarcinoma (n = 34; score, 0.86). bcl-2 expression did not correlate with stage, grade, estrogen-receptor, or progesterone-receptor expression. Polymerase chain reaction analyses of DNA isolated from several endometrial carcinomas were negative for (14;18) translocation involving the bcl-2 gene. Thus, bcl-2 apparently plays no role in the progression of atypical hyperplasia to carcinoma or in the development of high-grade or advanced-stage endometrial carcinoma. These results, however, do not rule out the involvement of bcl-2 in very early, preatypical hyperplasia phases of endometrial carcinogenesis. Finally, the marked difference in bcl-2 expression in hyperplastic and atypically hyperplastic glands might prove to be diagnostically useful in the often difficult distinction of these entities.

A five-year analysis of antimicrobial susceptibility testing profiles for beta-lactam antimicrobials, with inter-hospital and susceptibility method comparisons within a medical school affiliated hospital system.

A comparative study of antimicrobial susceptibility patterns was performed for a five-year period in four hospitals affiliated with the University of Utah School of Medicine due to concern that susceptibility testing method and results differences between hospital units might complicate training and comprise initial antimicrobial therapy. Few significant pattern changes were detected within or between the individual hospitals during the five-year period, and variances between hospitals were in general no greater than variances demonstrated within individual service units within the University Hospital.

Is vaginal douching related to cervical carcinoma?

The association between cervical carcinoma and vaginal douching was examined in a population-based case-control study conducted in the low-risk population of Utah between 1984 and 1987. The authors compared 266 cases of in situ and invasive cervical carcinoma with 408 group-matched controls by vaginal douching behavior, controlled for age, lifetime number of sex partners, cigarette smoking history, religious activity, and educational level. Essentially no association was found in women who douched once per week or less, but in those who douched more than once per week, a consistent relation was demonstrated (adjusted odds ratio = 4.7, 95% confidence interval 1.9-11). Few differences were found with type of douching preparation used. The authors hypothesize that frequent douching alters the vaginal chemical environment, making the cervix more susceptible to pathologic change.

Sexual activity, contraception, genital infections, and cervical cancer: support for a sexually transmitted disease hypothesis.

A case-control study was conducted in Utah between 1984 and 1987 to examine risk factors for cervical cancer. Interviews were completed with 266 histologically confirmed carcinoma in situ and invasive squamous cell cervical cancer cases who were categorically matched by age to 408 controls. Among the factors identified as altering risk for cervical cancer, after adjustment for age, education, church attendance, and cigarette smoking, were: having numerous sex partners (odds ratio (OR) = 8.99 for 10 or more partners); the current mate having several sex partners (adjusted OR for 10 or more partners = 8.62); using foam or jelly as a contraceptive method (OR, adjusted for number of sex partners, = 0.44); reported Trichomonas infection (OR, adjusted for number of sex partners, = 2.10); and herpes simplex virus type 2 infection as determined by 2:1 neutralization index values above 100 (OR = 2.70). A protective effect was noted from the use of diaphragms (OR = 0.67) or condoms (OR = 0.53) in women who reported more than one sex partner. These data support the hypothesis that cervical cancer is a sexually transmitted disease.

Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease.

Guinea pigs inoculated intravaginally with herpes simplex virus type 2 (HSV-2) developed a self-limiting infection characterized by vesiculo-ulcerative lesions on the external genital skin, urinary retention, and hindlimb paralysis. Infection rarely resulted in death. Virologic, histologic, and immunoperoxidase data suggested the following scheme for viral pathogenesis: initial replication in the introitus, vagina, and bladder; spread via sensory nerves to the lumbosacral dorsal root ganglia and spinal cord, and transmission via peripheral nerves to the external genital skin to produce the characteristic lesions. After recovery from primary infection, animals developed recurrent vesicular lesions, shed virus from genital sites in the absence of lesions, and harbored latent HSV-2 in dorsal root ganglia. Genital infection in the guinea pig shares many features with genital herpes in humans and provides a model to explore mechanisms of latency and reactivation and to evaluate several methods for control of recurrent disease.

Cigarette smoking and exposure to passive smoke are risk factors for cervical cancer.

Personal cigarette smoking and exposure to passive smoke as risk factors for cervical cancer were examined in a population-based, case-control study conducted in Utah. Personal cigarette smoking was found to increase the risk of cervical cancer, after adjusting for age, educational level, church attendance, and sexual activity. The adjusted risk estimate associated with being a current smoker was 3.42 (95% confidence interval [Cl], 2.10 to 5.57); for having smoked for 5 or more pack-years, it was 2.81 (95% Cl, 1.73 to 4.55); and for having smoked at least 100 lifetime cigarettes, it was 2.21 (95% Cl, 1.44 to 3.39). The adjusted risk estimate (also adjusted for actual cigarettes smoked) associated with passive smoke exposure for 3 or more hours per day was 2.96 (95% Cl, 1.25 to 7.03). Risk from passive smoking was greater in women who were not smokers (odds ratio, 3.43; 95% Cl, 1.23 to 9.54) than in women who smoked (odds ratio, 2.59; 95% Cl, 0.23 to 29.24).

Dietary vitamins A, C, and E and selenium as risk factors for cervical cancer.

The relation between cervical cancer and dietary intake of vitamins A, C, and E, beta-carotene, and selenium was examined in a population-based case-control study in Utah. Cervical cancer cases (n = 266) and population-based controls (n = 408) were interviewed between 1984 and 1987. Protective effects were observed for vitamins A, C, and E and beta-carotene but were attenuated by age, level of education, and lifetime cigarette use. Associated risk (comparing highest with lowest quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted) for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E; and from 0.95 (crude) to 0.70 (adjusted) for selenium. Adjustment for number of sex partners and church attendance, factors significantly related to cervical cancer risk, only slightly attenuated these adjusted risk estimates.

Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss.

We determined whether purified immunoglobulin G from patients with antiphospholipid antibodies causes fetal loss in pregnant mice. Sera were obtained from nonpregnant parous women (group 1) and nonpregnant women with antiphospholipid antibodies and a history of fetal loss (group 2). Pregnant BALB/c mice were given an intraperitoneal injection of 15 mg of IgG on day 8 of pregnancy. Typically, mice treated with IgG from antiphospholipid antibodies aborted within 48 hours. When animals were sacrificed on days 9 to 15, the uterus of each animal was inspected for the presence of live, dead, or resorbing fetuses. In contrast to mice injected with control IgG or saline solution, each mouse injected with IgG from antiphospholipid antibodies aborted and no live fetuses were found (p less than 0.05). Histologic examination of the uteroplacental interface showed decidual necrosis in the mice treated with IgG containing antiphospholipid antibodies, and immunofluorescent studies also showed prominent intravascular decidual IgG and fibrin deposition. We conclude that IgG from antiphospholipid antibodies of women with fetal loss causes fetal loss in BALB/c mice. It appears that the fetal loss is mediated by IgG binding in the maternal decidual vasculature.

Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals.

Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes. A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues. The skin button is designed to protect the tissues from damage and provide a secure material-tissue interface. Prevention of superficial and invasive infection is the primary goal of the skin button. Eight calves were studied prospectively to identify gross or microscopic infection with the skin button. All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection. All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation. No animal died secondary to a skin button infection. Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects.

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stage III, optimal disease ovarian cancer: a Southwest Oncology Group Study.

Between 1979 and 1984, 98 patients considered to have stage III epithelial type ovarian cancer and optimal surgical resections (i.e., less than 2 cm residual tumor masses) were randomly assigned to treatment with 2 cm residual tumor masses) were randomly assigned to treatment with doxorubicin + cyclophosphamide + BCG (DC + BCG) vs doxorubicin + cyclophosphamide + cisplatin (DCP) vs. doxorubicin + cyclophosphamide + cisplatin + BCG (DCP + BCG). Seventeen (17%) were considered ineligible on the basis of formal histopathologic review. The pathologically proven complete response rates for DC + BCG, DCP, and DCP + BCG-treated patients were 20, 23, and 41%, respectively, and the median survival durations were 36.8, 48.2, and 57.4 months, respectively. Because of the relatively small sample size, definite conclusions concerning the response or survival impact of adding cisplatin to DC + BCG or BCG to DCP can not be drawn; nevertheless, all three groups of patients experienced prolonged survival durations with approximately 40% of all eligible patients alive at 5 years.

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: a Southwest Oncology Group Study.

Between 1979 and 1984, 185 fully evaluable patients with stage III or IV epithelial type ovarian cancer and suboptimal surgical resections were randomly assigned to treatment with doxorubicin + cyclophosphamide + BCG (DC + BCG) vs doxorubicin + cyclophosphamide + cisplatin (DCP) vs. doxorubicin + cyclophosphamide + cisplatin + BCG (DCP + BCG). Patients with measurable disease (119) were analyzed separately from those with nonmeasurable disease (66). In measurable disease patients the overall clinical complete plus partial response rates for DC + BCG, DCP, and DCP + BCG-treated patients were 36, 57, and 59%, respectively. Although there were no significant patient characteristic differences between the DCP and DCP + BCG treatment groups, the addition of cisplatin to the DC + BCG regimen resulted in significantly prolonged response (P less than 0.03) and survival (P less than 0.002) durations. To the contrary, the addition of BCG to the DCP regimen did not improve objective response rates or response or survival durations. For patients with nonmeasurable, suboptimal disease there were no significant differences between the three treatments with respect to response or survival parameters; however, patients in this disease category fared generally better than those with clinically measurable disease. We conclude that cisplatin adds significantly to the efficacy of DC + BCG, but BCG does not add to the efficacy of DCP in patients with measurable, stage III or IV disease.