Results are presented of a harmonic analysis of the large-scale cosmic-ray (CR) anisotropy as observed by the Milagro observatory. We show a two-dimensional display of the sidereal anisotropy projections in right ascension (R.A.) generated by the fitting of three harmonics to 18 separate declination bands. The Milagro observatory is a water Cherenkov detector located in the Jemez mountains near Los Alamos, New Mexico. With a high duty cycle and large field of view, Milagro is an excellent instrument for measuring this anisotropy with high sensitivity at TeV energies. The analysis is conducted using a seven-year data sample consisting of more than 95 billion events, the largest such data set in existence. We observe an anisotropy with a magnitude around 0.1% for CRs with a median energy of 6 TeV. The dominant feature is a deficit region of depth (2.49 ± 0.02 stat. ± 0.09 sys.) ×10−3 in the direction of the Galactic north pole centered at 189 deg R.A. We observe a steady increase in the magnitude of the signal over seven years.

A survey of Galactic gamma-ray sources at a median energy of ~20 TeV has been performed using the Milagro Gamma-Ray Observatory. Eight candidate sources of TeV emission are detected with pretrial significances >4.5 σ in the region of Galactic longitude l ∊ [30°, 220°] and latitude b ∊ [-10°, 10°]. Four of these sources, including the Crab Nebula and the recently published MGRO J2019+37, are observed with significances >4 σ after accounting for the trials. All four of these sources are also coincident with EGRET sources. Two of the lower significance sources are coincident with EGRET sources, and one of these sources is Geminga. The other two candidates are in the Cygnus region of the Galaxy. Several of the sources appear to be spatially extended. The fluxes of the sources at 20 TeV range from ~25% of the Crab flux to nearly as bright as the Crab.

From the post-War period to the 1960s, immense changes took place in the philosophy, organization and delivery of mental health care in the UK. These changes were driven by the financial burden that Bevan's National Health Service imposed on the British Government, by the dynamism and vision of psychiatrists and mental health nurses returning from the War, and by a new social and cultural consciousness, which put minority groups such as the mentally ill onto the political agenda. This paper seeks to explore some of these complex interactions and to show how the closure of mental hospitals was the inevitable outcome of movements both inside psychiatry and far beyond it. An awareness of the historical context of mental health care can assist planners and providers to avoid the many pitfalls that have been made by our predecessors.

To evaluate the effects of changing steroid milieu on adrenocortical function, basal levels and responses of cortisol, 17-hydroxyprogesterone (17PO), androstenedione (A), dehydroepiandrosterone (DHEA), and testosterone to exogenous synthetic ACTH were investigated in six normal women during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle and in five women on an oral contraceptive (OC) agent (35 μg ethinyl estradiol and 1 mg ethynodiol diacetate, Demulen). Baseline serum steroid and cortisol binding globulin (CBG) levels were measured on days 3–7 and 21–23 of the menstrual cycle in the normal subjects and on days 3–7 of OC treatment cycles. ACTH stimulation (10μg m-2 i.v. bolus) was performed following dexamethasone suppression (0.5 mg p.o. q 6h×4). Basal levels of cortisol and CBG as well as cortisol responses to ACTH were increased in OC users relative to normal women tested during both the EF and ML phases of the cycle. In addition, 17PO levels were increased during the ML phase both before and following dexamethasone suppression compared to levels present in the EF phase and in OC users, no doubt because of increased ovarian steroidogenesis.

Because we previously found increased basal serum cortisol levels in women runners, we examined adrenocortical function in amenorrheic running women (AR), eumenorrheic running women (R), and normal nonexercising women (NC) in further detail. Mean 24-h urinary cortisol levels were significantly elevated (P less than 0.001) in six AR [45.1 +/- 7.2 (+/- SEM) micrograms/24 h] and eight R (38.5 +/- 6.9 micrograms/24 h) compared to four NC (13.9 +/- 2.8 micrograms/24 h). After adrenal suppression with 2 mg dexamethasone, integrated responses and absolute maximal elevations in serum cortisol levels in response to 10 micrograms/m2 exogenous ACTH (1-24) administered as an iv bolus dose, were not significantly different among six AR, six R, and six NC. This dose of ACTH results in maximal steroid release. The disappearance rates of cortisol (5 mg, iv) after dexamethasone suppression were similar in four AR, five R, and four NC and corresponded to a two-compartment model with mean half-lives of 4.9 and 93.8 min, respectively. Cortisol-binding globulin levels were also similar among the groups. These data document higher cortisol secretion and suggest increased ACTH secretion in running women.

The direct effects of estradiol (E2) and enclomiphene citrate on testicular LH/hCG receptor content, steroidogenesis and morphology were studied in immature, hypophysectomized rats treated with FSH. Treatment with FSH (100 µg bovine FSH for 5 days) caused a marked increase in testis weight. This increase was abolished by concomitant injections of E2 (1 or 10 µg), while concomitant treatment with enclomiphene citrate (1–100 µg) had no significant effect. The spermatogenesis maintained by FSH was inhibited by concomitant daily treatment with E2 (1 or 10µ g) or enclomiphene citrate (100 µg). FSH treatment increased the LH/hCG receptor content of the testis. Concomitant administration of E2 (1 or 10 µg) or a high dose of enclomiphene citrate (100 µg) abolished the FSH-induced increase in LH/hCG receptors. In vitro incubations of the testis demonstrated that FSH treatment caused a marked rise in basal and hCG-stimulated testosterone production whereas concomitant treatment with E2 or enclomiphene citrate inhibited the FSH stimulated increase in testosterone production. The steroidogenic responsiveness to hCG was markedly depressed by treatment with either 1 or 10 µg E2 (71 and 91% decreases, respectively). Likewise, treatment with 1 or 100 µg enclomiphene citrate decreased testosterone production by 32 and 60%, respectively. Associated with the decrease in testosterone production, marked suppression of androstenedione and dehydroepiandrosterone (DHEA) production was observed in animals treated with estradiol or enclomiphene citrate while that of the 17α-hydroxylated precursors was less severely affected. These steroidogenic changes were accompanied by accumulation of C2 1, steroid intermediates (progesterone and pregnenolone) suggesting that the inhibitory effect of E2 and enclomiphene citrate was associated with a defect in 17α-hydroxylase and/or 17–20 desmolase activity. The results of this study indicate that enclomiphene citrate, like E2, has a direct inhibitory effect on the testis. Low doses of these compounds inhibit testosterone production mediated via decreased steroidogenic enzyme activity, whereas high doses of these compounds further decrease testicular LH/hCG receptor content and spermatogenesis.

The first record of a microsporidian infection of a marine nematode, Metoncholaimus scissus, is reported. Infection occurs in most of the host tissues, particularly those in the posterior portion of the body. Microsporidia have not been found in esophageal tissue; nor have they been detected in the tissues of the excretory and Demanian systems. Infection occurs throughout the year with highest incidence in early spring. High incidence among marine nematodes suggests a possible role in transmission of microsporidia to various commercially important invertebrates. The parasite is assigned to the genus Pleistophora.

Quantitative alterations in urinary estrogen excretion and plasma progesterone content were studied throughout the menstrual cycle of rhesus monkeys (Macaca mulatto). Estrogen levels were determined in 3 normal monkeys using thin-layer and gas-liquid chromatography. Estrone was the principal estrogen found, with a range of excretion (μg/24 hr) as follows: onset of menstruation 1.51-3.50; midcycle peak 8.20-8.60; 2 days post peak 1.11-1.92. Estradiol-17β and estriol were excreted in smaller amounts, ranging from undetectable to 1.32 μg/24 hr for estradiol and approximately 0.2 μg/24 hr for estriol. A second, smaller rise in estrone excretion was seen in the luteal phase of the cycle. No predictable pattern was observed for estradiol-17β and estriol because of low excretion level. Modification of the above procedure made possible a 24-hr method for determination of estrone. In 11 additional animals, peak estrone excretion was correlated with ovulation by timed observation of the ovaries. Ovulation occurred 2 days after the estrone peak in 9 animals and at 3 days in 2 others. Thus, the estrone peak may provide a reliable indicator of ovulation time. Peripheral plasma progesterone concentrations and urinary estrone excretion during a normal menstrual cycle were determined for 4 monkeys. Progesterone was measured by a competitive protein binding technique. The post-peak nadir in estrone excretion, concomitant with the early rise in plasma progesterone, supports previous studies in which the rise in progesterone level was used to predict the time of ovulation in this species. (Endocrinology86: 1225, 1970)

Active Galaxies such as Mrk 421 have been shown to be highly variable at all time scales. Atmospheric Cherenkov Telescopes (ACTs) have excellent instantaneous sensitivity and have observed short bright flares from Mrk 421. However, long duration vari ability is difficult to monitor with ACTs due to their intermittent exposure. Milagro, in contrast, m onitors Mrk 421 with daily observations. While Milagro lacks the sensitivity to detect short duration flare s, it is capable of long duration monitoring of the total flux of Mrk 421 on time scales from months to years. In this paper we present the long duration variability and total fluence of Mrk 421 using 6 years of data f rom Milagro.