Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Extended Search for the Invisible Axion with the Axion Dark Matter Experiment.

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 µeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.

Search for Invisible Axion Dark Matter with the Axion Dark Matter Experiment.

This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81 µeV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses.

Piezoelectrically Tuned Multimode Cavity Search for Axion Dark Matter.

The µeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Axion Dark Matter Experiment: Detailed design and operations.

Axion dark matter experiment ultra-low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the 2.66-3.1 µeV mass range with Dine-Fischler-Srednicki-Zhitnisky sensitivity [Du et al., Phys. Rev. Lett. 120, 151301 (2018) and Braine et al., Phys. Rev. Lett. 124, 101303 (2020)]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as the state-of-the-art quantum-noise-limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable microstrip superconducting quantum interference device amplifier in run 1A, and a Josephson parametric amplifier in run 1B, along with novel analysis tools that characterize the system noise temperature.

The Advanced LIGO photon calibrators.

The two interferometers of the Laser Interferometry Gravitational-wave Observatory (LIGO) recently detected gravitational waves from the mergers of binary black hole systems. Accurate calibration of the output of these detectors was crucial for the observation of these events and the extraction of parameters of the sources. The principal tools used to calibrate the responses of the second-generation (Advanced) LIGO detectors to gravitational waves are systems based on radiation pressure and referred to as photon calibrators. These systems, which were completely redesigned for Advanced LIGO, include several significant upgrades that enable them to meet the calibration requirements of second-generation gravitational wave detectors in the new era of gravitational-wave astronomy. We report on the design, implementation, and operation of these Advanced LIGO photon calibrators that are currently providing fiducial displacements on the order of 10-18m/Hz with accuracy and precision of better than 1%.

The effects of risedronate on canine cancellous bone remodeling: three-dimensional kinetic reconstruction of the remodeling site.

To investigate the dose-dependent effects of risedronate on cancellous bone remodeling, adult female beagle dogs were treated with either placebo, 0.1, 0.5, or 2.5 mg/kg/day of risedronate orally in an intermittent cyclic regimen (7 days on 21 days off), repeated three times. Iliac cancellous bone samples were subjected to histomorphometric analysis and three-dimensional (3-D) kinetic reconstruction of the remodeling site was performed. In the 0.1 mg/kg dose group, resorption and activation indices were no different from the placebo group. However, wall thickness was increased resulting in a positive bone balance at the level of the remodeling unit. In the 0.5 and 2.5 mg/kg dose groups, a dose-dependent reduction in activation frequency and tissue level bone formation was observed. Resorption rates were also significantly decreased, 60% and 80% for the 0.5- and 2.5-mg/kg groups, respectively. An approximate 25% reduction in final erosion depth was noted in both these groups. Analyses of the growth curves of the bone packet confirmed that the kinetics of the growth of a completed packet were different in the 0.5- and 2.5-mg/kg dose groups compared with placebo. These changes were associated with a significant increase in the final wall thickness in both groups indicating no net impairment of osteoblast function. These increases in wall thickness in combination with the reductions in final erosion depth in the 0.5 and 2.5 mg/kg groups resulted in a significant dose-dependent positive bone balance. This pharmacological profile suggests that risedronate may be of therapeutic utility in the treatment of metabolic bone diseases where reductions in activation frequency and resorptive cell activity at the level of the remodeling unit are a therapeutic goal.

Effect of erythropoietin on renal excretion of a sodium load.

To determine whether erythropoietin alters the renal excretion of a sodium load in humans, we administered either erythropoietin (150 units/kg) or vehicle intravenously in a randomized crossover design to six normal white men on day 4 of a controlled sodium diet. After erythropoietin administration, the subjects were given 2 L normal saline solution intravenously over 4 hours. All urine was collected for 4 days after drug administration. Serum sodium and creatinine levels and blood pressure were determined 0, 4, 8, and 24 hours after drug administration. Peripheral renin activity and aldosterone levels were determined 0, 4, and 8 hours after drug administration. Erythropoietin significantly decreased total sodium excretion during the 4 days after drug administration (erythropoietin = 784 +/- 46 mEq/4 days versus control = 840 +/- 41 mEq/4 days; p < 0.001). Erythropoietin did not alter creatinine clearance, blood pressure, or the changes in plasma renin activity and aldosterone caused by the saline load. We conclude that erythropoietin decreases urine sodium excretion after a sodium load in normal human subjects without altering glomerular filtration rate, blood pressure, or plasma renin activity.

Unclear speech: recognition and significance of unintelligible speech in preschool children.

Clarity of speech normally improves throughout the first few years of life, with acquisition of complete intelligibility by 4 years of age. Delayed emergence of intelligibility, or frankly unintelligible speech, often signify the presence of a major disturbance of language, overall cognitive development, or hearing. Norms are provided for the ages by which a child should be 50%, 75%, and 100% intelligible to strangers, and a new technique for screening intelligibility of speech is described. Data validating this technique are presented, and the developmental implications of unintelligible speech are reported. The importance of screening for intelligibility of speech is emphasized, in light of the findings presented.

Quantifying language development from birth to 3 years using the Early Language Milestone Scale.

A point-scoring technique for the Early Language Milestone Scale is described. Normative data based on the original 1982 cross-sectional sample and validation data based on a separate longitudinal sample are presented. Mean Early Language Milestone Scale point scores, standard deviations, and percentile equivalents for raw point scores are presented for all ages from birth to 36 months. Correlations between point scores on the Early Language Milestone Scale and scores on other standardized developmental tests such as the Stanford-Binet Intelligence Scale, the Peabody Picture Vocabulary Test, and the Illinois Test of Psycholinguistic Abilities are presented. The clinical and research advantages of this point-scoring technique are presented and compared with the original pass/fail scoring method.

Validation of an early language milestone scale in a high-risk population.

Detailed language evaluations were obtained by interviewing the parents of 191 healthy children aged 0 to 3 years, and by testing the children themselves. From these data, normative values were derived for 41 language milestones in the first 36 months of life. These values were used to construct the Early Language Milestone Scale (ELM Scale), a brief language assessment tool suitable for use by general pediatricians. Physician use of the ELM Scale in a population of 119 children considered at high risk for the presence of developmental disability yielded 97% sensitivity and 93% specificity for the ELM Scale as a detector of developmentally delayed children, when compared with more formal developmental measures as applied by a clinical psychologist or speech pathologist. Early language milestones are a sensitive indicator of developmental integrity; delayed achievement of early language milestones strongly suggests the presence of a significant underlying developmental disability. The ELM Scale may be adopted as a valid measure of developmental status among children considred at high risk for the presence of developmental disabilities.

Innervated liver plays an inhibitory role in regulation of food intake.

BACKGROUND: With the onset of eating, the associated rise of dopamine in the lateral hypothalamus (LHA-DA) is thought to regulate quantity of food consumed per meal. Early release of LHA-DA induced by eating is facilitated by oronasal stimulation; we propose that the subsequent LHA-DA response induced by nutrients in the portal vein is dampened by the innervated liver. This was tested by measuring LHA-DA in normal rats: during parenteral feeding to bypass oronasal stimulation, while eating during parenteral feeding, and while eating only. METHODS: Rats had either total liver denervation or sham operation, with placement of a jugular vein catheter and LHA-DA microdialysis cannula. After a 3-week recovery period total liver denervated rats were randomized to parenterally fed, food only, and parenteral plus food groups each with sham-operated controls in which LHA-DA was measured. RESULTS: No difference in LHA-DA release in food only groups occurred between total liver denervated or sham-operated rats. A significantly higher rise in LHA-DA was observed in total liver denervated versus sham-operated rats in parenterally fed (129% +/- 4% versus 116% +/- 2%; p < 0.05) and parenteral plus food (151% +/- 4% versus 134% +/- 4%; p < 0.05) groups. CONCLUSIONS: In total liver denervation versus sham operation, an increase in LHA-DA release occurs during parenteral feeding and eating during parenteral feeding, suggesting that innervated liver inhibits LHA-DA release.

Temporal changes in meal number and meal size relationship in response to rHu IL-1 alpha.

Peripherally infused interleukin-1 reduces food intake. Its temporal and selective effects on meal number and meal size were investigated in seven rats continuously infused for 3 days with recombinant human interleukin-1 alpha (rHu IL-1 alpha; 3 micrograms day-1, i.v.). Food intake decreased significantly during the first two infusion days, and was brought about by first the early reduction of meal number, followed by meal size with a 1 day delay. The primary effect of rHu IL-1 alpha was seen during the dark cycle. After the infusion was stopped, meal number recovered most quickly, followed by a lag in recovery of meal size. We conclude that rHu IL-1 alpha influenced food intake primarily via an effect on meal number, which responds more rapidly than a decrease in meal size, thereby inducing an immediate decrease in food intake.

Acute adaptive changes in food intake pattern following olfactory ablation in rats.

We determined whether acute compensatory feeding pattern changes after bulbectomy persist on a chronic basis, or whether physiological adaptation occurs to normalize acute changes. Rats were randomized to olfactory bulbectomy or sham operation; all had jugular vein catheterization. Food intake, meal number and size were studied during infusion of parenteral nutrients providing 100% daily caloric intake (PN-100) to minimize post-ingestive effects. Rats were randomly assigned to acute (from day 14 after operation, PN-100 infused for 4 days, followed by 4 days of saline infusion) or chronic study (PN-100 infused for 4 days from day 40, followed by 4 days of saline infusion). After olfactory ablation, acutely decreased meal size was offset by increased meal number, but 40 days after, baseline differences between meal size and number no longer existed. No qualitative differences in response to PN-100 were noted between acute and chronic groups. Findings suggest a functional adaptation of food intake regulatory mechanism between 14 and 40 days after bulbectomy.

Using information, motivational enhancement, and skills training to reduce the risk of HIV infection for low-income urban women: a second randomized clinical trial.

This randomized clinical trial evaluated an HIV-risk reduction (HIV-RR) intervention based on the information-motivation-behavioral skills model. At baseline, 102 women (M age = 29 years; 88% African American) completed a survey regarding HIV-related knowledge, risk perceptions, behavioral intentions, and risk behavior. Participants were then assigned to either the HIV-RR intervention or a health-promotion control group. Postintervention and follow-up data indicated that women in the HIV-RR program enhanced their knowledge and strengthened their risk reduction intentions relative to controls. Moreover, HIV-RR women who expressed "imperfect" intentions also increased their condom use, talked more with partners about condom use and HIV testing, and were more likely to have refused unprotected sex.

Olfactory bulbectomy in rats modulates feeding pattern but not total food intake.

The role of olfactory input in the regulation of food intake and feeding patterns in rats was investigated by performing bilateral olfactory bulbectomy. Compared to control rats, bulbectomized rats ate the same amounts of food, but did so via a decrease in meal size, and a doubling in meal number. Although no increase in meal duration occurred, the exploratory behavior of sniffing during meals and between meals also increased significantly. While it is not yet clear how the olfactory bulbs participate in regulating food intake configuration resulting in changed feeding patterns, their clinical role can be appreciated by observing the acute changes in feeding pattern that occur when their input to the lateral hypothalamic area is damaged experimentally.

Lack of influence of hysterectomy on meal size and meal number in Fischer-344 rats.

Based on our previous observation that, when eating the same amount of food per 100 g b.wt., male rats gain five to seven times more weight than females who have an estrous cycle every 4 to 5 days, we questioned whether lower weight gain seen in female rats could be the result of increased energy cost in preparing endometrium for anticipated fertilization. Because the uterus modulates estrogenic effects on other hormone-dependent behaviors, for example, sexual receptivity and lordosis, we performed this study to determine if estrogen-mediated cyclical changes in food intake and feeding pattern occur after hysterectomy. Fifteen female Fischer 344 rats were randomized during the estrous phase to either hysterectomy with ovarian preservation or sham operation. A rat eater meter was used to continuously measure food intake, meal number, and meal size for two estrous cycles before and four cycles after surgery. Both groups showed the estrous phase linked cycling in meal number, meal size, and food intake. No differences existed between the two groups in these indices either before or after surgery. No differences existed between groups in rate of body weight gain after surgery, 0.95 +/- 0.13 g/day in hysterectomized and 0.77 +/- 0.1 g/day in sham-operated rats. We conclude that hysterectomy has no effect on rate of weight gain, food intake, and estrus linked cyclical feeding pattern in Fischer 344 rats.

Change in meal size, number and duration after neural isolation of liver and with TPN.

The abundant neural connections between the liver and hypothalamus suggest that the liver contributes to spontaneous food intake (SFI) regulation. This hypothesis was tested in rats after total liver denervation (TLD) and infusing TPN. A sham operation (SO) or TLD was performed in Fischer rats, placed in metabolic cages fitted with an Eater Meter to measure SFI, meal number (MN), size (MZ), and duration (MD). Rats had free access to chow and water. After 22 days, a jugular catheter was placed and normal saline continuously infused for 10 days (days 22-32). Then TPN-100, providing 100% of rats daily energy needs, was infused for 3 days (days 32-35). During the post-SO/TLD and postjugular catheterization periods and during TPN-100, SFI was the same in SO controls and TLD group. However, TLD rats had decreased MZ and MD (interpreted as early satiety) and increased MN (interpreted as increased hunger) to maintain the same SFI as control rats. Although total SFI was not influenced by TLD, it significantly affected feeding pattern, suggesting that the neural isolation of the liver from the brain produces altered hypothalamic regulation of not only the onset of feeding, but also satiety.