First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Significant Excess of Electronlike Events in the MiniBooNE Short-Baseline Neutrino Experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions.

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

Observation of coherent elastic neutrino-nucleus scattering.

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

Dark Matter Search in a Proton Beam Dump with MiniBooNE.

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01

Medication safety in the operating room: literature and expert-based recommendations.

Human error poses significant risk for hospitalized patients causing an estimated 100,000 to 400,000 deaths in the USA annually. Medication errors contribute, with error occurring in 5.3% of medication administrations during surgery. In this study 70.3% of medication errors were deemed preventable. Given the paucity of randomized controlled studies, we undertook a rigorous review of the literature to identify recommendations supported by expert opinions. An extensive literature search pertaining to medication error, medication safety, operating room, and anaesthesia was performed. The National Guidelines Clearinghouse was searched for any anaesthesia or operating room medication safety guidelines.A total of 74 articles were included. Recommendations were tabulated and assigned points based on a scale revised from a prior study. A total of 138 unique recommendations were identified, with point tallies ranging from 4 to 190. An in-person focus meeting occurred, where the 138 recommendations were reviewed, combined and condensed. A modified Delphi process was used to eliminate items found to be unimportant or those unable to be quantified (e.g. "minimize fatigue"). A total of 35 specific recommendations remained. Adverse events as a result of medication errors occur frequently in the operative setting. There are few rigorous studies to direct medication safety strategies, but this should not lead us to do nothing. The overwhelming consensus regarding best practices should be accepted, and the recommendations implemented. Our list of recommended strategies can hopefully be used to assess local vulnerabilities and institute system solutions.

Precision Measurement of the Radiative ß Decay of the Free Neutron.

The standard model predicts that, in addition to a proton, an electron, and an antineutrino, a continuous spectrum of photons is emitted in the ß decay of the free neutron. We report on the RDK II experiment which measured the photon spectrum using two different detector arrays. An annular array of bismuth germanium oxide scintillators detected photons from 14 to 782 keV. The spectral shape was consistent with theory, and we determined a branching ratio of 0.00335±0.00005[stat]±0.00015[syst]. A second detector array of large area avalanche photodiodes directly detected photons from 0.4 to 14 keV. For this array, the spectral shape was consistent with theory, and the branching ratio was determined to be 0.00582±0.00023[stat]±0.00062[syst]. We report the first precision test of the shape of the photon energy spectrum from neutron radiative decay and a substantially improved determination of the branching ratio over a broad range of photon energies.

Physiological separation of vesicle pools in low- and high-output nerve terminals.

Physiological differences in low- (tonic like) and high-output (phasic like) synapses match many of the expected anatomical features of these terminals. However, investigation in the recruitment of synaptic vesicles from a reserve pool (RP) to a readily releasable pool (RRP) of synaptic vesicles within these types of nerve terminals has not been fully addressed. This study highlights physiological differences and differential modulation of the vesicles in a RP for maintaining synaptic output during evoked depression of the RRP. With the use of bafilomycin A1, a vacuolar ATPase blocker, recycling vesicles are blocked in refilling with transmitter. The tonic terminal is fatigue resistant due to a large RRP, whereas the phasic depresses rapidly upon continuous stimulation. These differences in rates of depression appear to be in the size and degree of utilization of the RRP of vesicles. The working model is that upon depression of the tonic terminal, serotonin (5-HT) has a large RP to act on in order to recruit vesicles to the RRP; whereas, the phasic terminal, 5-HT can recruit RP vesicles to the RRP prior to synaptic depression but not after depression. The vesicle pools are physiologically differentiated between phasic and tonic output terminals.

The regulation and packaging of synaptic vesicles as related to recruitment within glutamatergic synapses.

The reserve pool (RP) and readily releasable pool (RRP) of synaptic vesicles within presynaptic nerve terminals, at crayfish and larval Drosophila neuromuscular junctions (NMJs), were examined for physiological differentiation into distinctly separate functional groups. These NMJs are glutamatergic and produce graded excitatory postsynaptic potentials (EPSPs). The packaging of glutamate was perturbed by blocking the vesicular glutamate transporter (VGlut) with bafilomycin A1. Various frequencies of motor nerve stimulation, exposure time, and concentration of bafilomycin A1 were examined. The low-output tonic opener NMJs in crayfish exposed to 4 µM bafilomycin A1 and 20-Hz continuous stimulation decreased the EPSP amplitude to 50% in ∼30 min with controls lasting 3h. After activity and bafilomycin A1-induced synaptic depression, the EPSPs were rapidly revitalized by serotonin (5-HT, 1 µM) in the crayfish preparations. The 5-HT action can be blocked with a PLC inhibitor. We postulate 5-HT recruits unused vesicles from the RP. The perception is the RRP is selectively activated during rapid electrical stimulation (20 Hz) sparing the RP. When stimulation frequency is high (40 Hz) the RP is recruited to the RRP and dampens subsequent recruitment with 5-HT. The higher output synapses of the larval Drosophila NMJ when stimulated at 1 Hz or 5 Hz and exposed to 4 µM of bafilomycin A1 showed a depression rate of 50% within ∼10 min with controls lasting ∼40 min. After low frequency depression and/or exposure to bafilomycin A1 a burst of higher frequency (10 Hz) can recruit vesicles from the RP to the RRP.

New limit on time-reversal violation in beta decay.

We report the results of an improved determination of the triple correlation DP·(p(e)×p(v)) that can be used to limit possible time-reversal invariance in the beta decay of polarized neutrons and constrain extensions to the standard model. Our result is D=[-0.96±1.89(stat)±1.01(sys)]×10(-4). The corresponding phase between gA and gV is ϕAV=180.013°±0.028° (68% confidence level). This result represents the most sensitive measurement of D in nuclear ß decay.

Immune response and blood chemistry of pigs fed conjugated linoleic acid.

Immune function (response to concanavalin A, cytokine production, and lymphocyte profiles) and blood chemistry variables were measured in growing-finishing pigs (Yorkshire/Landrace/Duroc dam × Hampshire sire) fed varying percentages of CLA (0, 0.12, 0.25, 0.50, and 1.0%). Blood was collected at 0, 14, 28, 42, and 56 d on feed (DOF). Total white blood cell (WBC) count increased (P < 0.01) linearly to 42 DOF. No differences (P = 0.53) were observed for WBC across CLA treatment. Nitric oxide was greater (P < 0.01) for the 1.0% CLA treatment compared with all other treatments. Flow cytometry using fluorescent labeled monoclonal antibodies to the CD4, CD8, double-positive CD4/CD8, and CD2 surface markers was used to determine lymphocyte subpopulations. Supplementation of CLA had no effect (P = 0.61) on lymphocyte subpopulation cell distribution. Most blood chemistry variables were within the normal metabolic range for pigs. A decrease was observed over DOF for P (P < 0.01) and K (P < 0.05). Additionally, Na and Cl concentrations increased (P < 0.05) from 14 to 28 DOF and decreased over the remainder of the trial. Electrolyte balance was not different (P = 0.38) across CLA treatments and was likely explained by no differences in feed intake among the CLA treatment groups. Blood lipid variables indicated that total cholesterol (P < 0.001), triglycerides (P < 0.001), high-density lipoproteins (P < 0.001), and low-density lipoproteins (P < 0.01) increased as the amount of CLA in the diet increased, but none of the results from these treatments exceeded the normal range of acceptability. These results suggested that CLA was safe when fed to growing-finishing pigs and had little effect on their immune function and blood chemistry variables.

Peritoneal dialysis in cats with acute kidney injury: 22 cases (2001-2006).

BACKGROUND: Peritoneal dialysis (PD) has been described for use in animals with acute kidney injury refractory to fluid therapy. However, no study has examined the use of PD in a large group of cats. HYPOTHESIS: PD is an important adjunctive therapy to treat acute kidney injury in cats. ANIMALS: The medical records of 22 cats with acute kidney injury that had received PD were examined. Animals were excluded if acute uremia was a result of postrenal causes such as uroabdomen or urethral obstruction. METHODS: Medical records were reviewed for the following: indication for PD, outcome, number of cycles performed, survival time, and predialysis and postdialysis results for blood urea nitrogen (BUN), creatinine, potassium, chloride, sodium, phosphorus, total protein, and albumin concentrations, and urine output. RESULTS: Indications for PD include acute-on-chronic kidney injury, acute kidney injury caused by toxins, bilateral ureteroliths, bilateral ureteral ligation as a complication of ovariohysterectomy, and unknown causes. The median survival time for all cats on PD was 4 days, although the median survival time for the cats that were discharged was 774 days. The most common complications were dialysate retention and sequestration of dialysate SC. There was a significant (P < .05) decrease between predialysis and postdialysis results for BUN, creatinine, potassium, phosphorus, total protein, and albumin concentrations. There was a significant (P < .05) difference in survival times between sexes. CONCLUSIONS AND CLINICAL IMPORTANCE: PD is an effective option for treatment of cats with acute kidney injury refractory to fluid therapy.

Structure/function assessment of synapses at motor nerve terminals.

The release of transmitter at neuromuscular junctions (NMJ) of the opener muscle in crayfish is quantal in nature. This NMJ offers the advantage of being able to record quantal events at specific visually identified release sites, thus allowing measurement of the physiological parameters of vesicle release and its response to be directly correlated with synaptic structure. These experiments take advantage of areas between the varicosities on the nerve terminal that we define as "stems." Stems were chosen as the region to study because of their low synaptic output due to fewer synaptic sites. Through 3D reconstruction from hundreds of serial sections, obtained by transmission electron microscopy (TEM), at a site in which focal macropatch recordings were obtained, the number of synapses and AZs are revealed. Thus, physiological profiles with various stimulation conditions can be assessed in regards to direct synaptic structure. Here, we used the properties of the quantal shape to determine if distinct subsets of quantal signatures existed and if differences in the distributions are present depending on the frequency of stimulation. Such a quantal signature could come about by parameters of area, rise time, peak amplitude, latency, and tau decay. In this study, it is shown that even at defined sites on the stem, with few active zones, synaptic transmission is still complex and the quantal responses appear to be variable even for a given synapse over time. In this study, we could not identify a quantal signature for the conditions utilized.

The effects of acute carbon dioxide on behavior and physiology in Procambarus clarkii.

Vertebrates and invertebrates show a similar response of rapid anesthesia with high levels of carbon dioxide. In this study, we use crayfish to examine both behavioral and physiological responses to increasing [CO(2)] to explain the rapid unresponsiveness and cessation of an autonomic response. Hypoxic and low pH environments that are induced by CO(2) exposure were also examined, although neither produced the identified CO(2) effects. In insects, low concentrations play a vital role in providing information for task performance such as food location through attraction cues, whereas high concentrations produce avoidance responses. We found behavioral responses in crayfish that demonstrate a strong repellent effect to high [CO(2)] and that the avoidance behavior decreases with lower [CO(2)]. There was not a preference and/or repellent behavioral response with 5% CO(2), hypoxic or low pH environments. Mechanosensory stimulation showed that only at high [CO(2)] there is an unresponsiveness to stimuli within a 30 min time period. Additionally, the autonomic bioindex of heart and ventilatory rates showed a complete cessation with high acute exposure within in the same time period for unresponsiveness to mechanosensory stimulation.

Furthering pharmacological and physiological assessment of the glutamatergic receptors at the Drosophila neuromuscular junction.

Drosophila melanogaster larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequences of the postsynaptic glutamate receptors have been described; however, the pharmacological profile has not been fully elucidated. The postsynaptic molecular sequence suggests a novel glutamate receptor subtype. Kainate does not depolarize the muscle, but dampens evoked EPSP amplitudes. Quantal responses show a decreased amplitude and area under the voltage curve indicative of reduced postsynaptic receptor sensitivity to glutamate transmission. ATPA, a kainate receptor agonist, did not mimic kainate's action. The metabotropic glutamate receptor agonist t-ACPD had no effect. Domoic acid, a kainate/AMPA receptor agonist, blocks the postsynaptic receptors without depolarizing the muscle. However, SYM 2081, a kainate receptor agonist, did depolarize the muscle and reduce the EPSP amplitude at 1 mM but not at 0.1 mM. This supports the notion that these are generally a quisqualate subtype receptors with some oddities in the pharmacological profile. The results suggest a direct postsynaptic action of kainate due to partial antagonist action on the quisqualate receptors. There does not appear to be presynaptic auto-regulation via a kainate receptor subtype or a metabotropic auto-receptor. This study aids in furthering the pharmokinetic profiling and specificity of the receptor subtypes.

Reproductive effects of maternal and pre-weaning undernutrition in rat offspring: age at puberty, onset of female reproductive senescence and intergenerational pup growth and viability.

Maternal and/or postnatal undernutrition are widespread in human populations and are components of many experimental developmental and reproductive toxicology bio-assays. This study investigated in utero and/or pre-weaning undernutrition effects on reproductive maturation and senescence in the Sprague-Dawley rat as well as potential intergenerational effects. Pregnant rats were given food ad libitum or at 50% of normal dietary intake throughout pregnancy. Their offspring (control or IUGR) were cross-fostered to control dams with litter sizes of 8 or 16 pups (control and undernourished). Offspring body weights were reduced and onset of male puberty slightly delayed in animals from large postnatal litters. Similar body weight effects were observed in females but there was no difference in the age of vaginal opening. Female reproductive senescence as measured by onset of estrus acyclicity occurred at a younger age in IUGR-8-pup and Control-16-pup groups compared to Control-8-pup or IUGR-16-pup groups. Females were bred to control males and no evidence of adverse reproductive effects was found in any F2 groups. The offspring of the F1 generation did not show an intergenerational effect as documented in humans.

Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat.

Previous data have shown that regional differences in the presence of anterior pituitary luteinizing hormone (LH) generally correlate with the comparable disparities in distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estrous cycle, but are more prominent during the hours preceding the proestrus surge of LH. The current experiments examined (1) if such regional disparities are present throughout the surge window, (2) if differences are mirrored by release of LH in vitro and (3) if the appearance of regional differences is altered in ovariectomized females. Results showed that a comparative elevation in the rostral portion of the pituitary during the pre-surge period diminishes and finally disappears concurrent with the rise in circulating LH. This increase in rostral LH concentrations is reflected in this region by a comparable effect in vitro on stimulated LH secretion from pituitary fragments, although the effect is somewhat diminished by referencing release against tissue concentrations of LH present in a contralateral rostral fragment. Ovariectomies conducted at 1500h on proestrus, at a time when a significant regional difference has faded, resulted in a prompt increase in LH across all areas of the pituitary, and the emergence of a marked augmentation in rostral concentrations over the ensuing 72h. The effect was not seen when ovariectomies were performed on estrus. These data show that, while a regional disparity in anterior pituitary LH is present as circulating concentrations of estradiol rise prior to the LH surge, the removal of this steroid feedback at a time when LH synthesis is normally amplified accentuates the difference between the rostral region and other areas of the pituitary.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.