Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

α -event characterization and rejection in point-contact HPGe detectors.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0 ν ß ß ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0 ν ß ß region of interest window by an order of magnitude in the Majorana Demonstrator  and will be used in the upcoming LEGEND-200 experiment.

A hypothesis-driven weight-of-evidence analysis to evaluate potential endocrine activity of perfluorohexanoic acid.

Perfluorohexanoic acid (PFHxA) is a potential impurity and environmental degradation product of C6-based fluorotelomer products. Considering the potential endocrine activity of perfluoroalkyl acids, a hypothesis-driven weight-of-evidence (WoE) analysis was conducted to evaluate the potential endocrine disruptor activity of PFHxA, as defined by World Health Organization (WHO), across estrogen (E), androgen (A), thyroid (T), and steroidogenesis (S) pathways. A comprehensive literature search identified primary and secondary studies across species for review. The ToxCast/Tox21 database provided in vitro data. Studies identified were reviewed for reliability, and relevance, with endocrine endpoints ranked, and lines of evidence evaluated across pathways. Overall, PFHxA showed no endocrine effects in Japanese medaka, juvenile rainbow trout, chickens or reproductive parameters in northern bobwhite with no significant activity in rodent repeated-dose toxicity, lifetime cancer, or reproductive and developmental studies. In vitro, there was weak or negative activity for T transport protein or activation of E, A or T receptors. PFHxA was also negative in vitro and in vivo for disrupting steroidogenesis. Based on this WoE endocrine analysis, PFHxA exposure did not cause adverse effects associated with alterations in endocrine activity in these models, as such would not be characterized as an endocrine disruptor according to the WHO definition.

First Limit on the Direct Detection of Lightly Ionizing Particles for Electric Charge as Low as e/1000 with the Majorana Demonstrator.

The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in ^{76}Ge. The heavily shielded array of germanium detectors, placed nearly a mile underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. Free, relativistic, lightly ionizing particles with an electrical charge less than e are forbidden by the standard model but predicted by some of its extensions. If such particles exist, they might be detected in the Majorana Demonstrator by searching for multiple-detector events with individual-detector energy depositions down to 1 keV. This search is background-free, and no candidate events have been found in 285 days of data taking. New direct-detection limits are set for the flux of lightly ionizing particles for charges as low as e/1000.

New Limits on Bosonic Dark Matter, Solar Axions, Pauli Exclusion Principle Violation, and Electron Decay from the Majorana Demonstrator.

We present new limits on exotic keV-scale physics based on 478 kg d of Majorana Demonstrator commissioning data. Constraints at the 90% confidence level are derived on bosonic dark matter (DM) and solar axion couplings, Pauli exclusion principle violating (PEPV) decay, and electron decay using monoenergetic peak signal limits above our background. Our most stringent DM constraints are set for 11.8 keV mass particles, limiting g_{Ae}<4.5×10^{-13} for pseudoscalars and (α^{'}/α)<9.7×10^{-28} for vectors. We also report a 14.4 keV solar axion coupling limit of g_{AN}^{eff}×g_{Ae}<3.8×10^{-17}, a 1/2ß^{2}<8.5×10^{-48} limit on the strength of PEPV electron transitions, and a lower limit on the electron lifetime of τ_{e}>1.2×10^{24} yr for e^{-}→ invisible.

A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework.

TBBPA is a non-genotoxic flame retardant used to improve fire safety in a wide variety of consumer products. Estimated human exposures to TBBPA are very low (<0.000084 mg/kg-day), relative to the doses (500 and 1000 mg/kg-day of TBBPA) administered in a recent bioassay that resulted in uterine tumors in Wistar Han rats following chronic exposure. As part of an effort to characterize the relevance of the uterine tumors to humans, data and biological knowledge relevant to the progression of events associated with TBBPA-induced uterine tumors in female rats were organized in an adverse outcome pathway (AOP) framework. Based on a review of possible MOAs for chemically induced uterine tumors and available TBBPA data sets, a plausible molecular initiating event (MIE) was the ability of TBBPA to bind to and inhibit estrogen sulfotransferases, the enzymes responsible for sulfation of estradiol. Subsequent key events in the AOP, including increased bioavailability of unconjugated estrogens in uterine tissue, would occur as a result of decreased sulfation, leading to a disruption in estrogen homeostasis, increased expression of estrogen responsive genes, cell proliferation, and hyperplasia. Available data support subsequent key events, including generation of reactive quinones from the metabolism of estrogens, followed by DNA damage that could contribute to the development of uterine tumors. Uncertainties associated with human relevance are highlighted by potential strain/species sensitivities to development of uterine tumors, as well as the characterization of a dose-dependent MIE. For the latter, it was determined that the TBBPA metabolic profile is altered at high doses (such as those used in the cancer bioassay), and thus an MIE that is only operative under repeated high dose, administration. The MIE and subsequent key events for the development of TBBPA-induced uterine tumors are not feasible in humans given differences in the kinetic and dynamic factors associated with high dose exposures in rats relative to human exposure levels to TBBPA.

[OCT and PVEP examination in eyes with visible idiopathic optic disc drusen]. / Nachweis einer Neuropathie bei Drusen der Papille mittels der visuell evozierten Potenziale (VEP) und optischen Kohärenztomographie (OCT).

OBJECTIVES: It has been reported that the presence of optic disc drusen is mostly not associated with a reduction in function of the visual organ. At present by using more precise diagnostic tools it is possible to find more pathology. The aim of the study was to evaluate changes in peripapillar RNFL thickness and VEP parameters in a group of patients at the Department of Ophthalmology in Poznan, with diagnosed visible idiopathic optic disc drusen. MATERIALS AND METHODS: We have reviewed the medical records of 7 patients (5 women and 2 men) age range 43 - 61 years, mean age 51 years, with idiopathic visible optic disc drusen confirmed by ultrasound B scan. RNFL were measured with use of an OCT system (Stratus, Zeiss): fast RNFL thickness = 3.4. VEP were evaluated with use of a 60 pattern. RESULTS: In all patients OCT has shown a thinnig of peripapillar retinal nerve fiber layer. The lowest values were found in the superior and inferior quadrants. In 9 eyes we recorded VEPs with prolonged latency P100 from 117.2 - 135.8 msec, with a small reduction of the P100 amplitude. CONCLUSIONS: Idiopathic visible optic disc drusen are associated with changes in peripapillar RNFL thickness, especially in the superior and inferior quadrants. The anatomic pathology is related to functional abnormalities as confirmed with VEP. Detection of this type of drusen should be an indication to search for possible RNFL and VEP pathologies and to monitor their possible progression.

Convergence of auditory-nerve fiber projections onto globular bushy cells.

Globular bushy cells are a key element of brainstem circuits that mediate the early stages of sound localization. Many of their physiological properties have been attributed to convergence of inputs from the auditory nerve, many of which are large with complex geometry, but the number of these terminals contacting individual cells has not been measured directly. Herein we report, using cats as the experimental model, that this number ranged greatly (9-69) across a population of 12 cells, but over one-half of the cells (seven of 12) received between 15 and 23 inputs. In addition, we provide the first measurements of cell body surface area, which also varies considerably within this population and is uncorrelated with convergence. For one cell, we were able to document axonal structure over a distance greater than 100 microm, between the soma and the location where the axon expanded to its characteristic large diameter. These data were combined with accumulated physiological information on vesicle release, receptor kinetics and voltage-gated ionic conductances, and incorporated into computational models for four cells that are representative of the structural variation within our sample population. This predictive model reveals that basic physiological features, such as precise first spike latencies and peristimulus time histogram shapes, including primary-like with notch and onset-L, can be generated in these cells without including inhibitory inputs. However, phase-locking is not significantly enhanced over auditory-nerve fibers. These combined anatomical and computational approaches reveal additional parameters, such as active zone density, nerve terminal size, numbers and sources of inhibitory inputs and their activity patterns, that must be determined and incorporated into next-generation models to understand the physiology of globular bushy cells.

Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) exhibit an adverse cardiovascular risk profile, characteristic of the metabolic cardiovascular syndrome (MCS). The aim of this study was to determine the prevalence of coronary artery (CAC) and aortic (AC) calcification among middle-aged PCOS cases and controls and to explore the relationship among calcification, MCS, and other cardiovascular risk factors assessed 9 yr earlier. This was a prospective study of 61 PCOS cases and 85 similarly aged controls screened in 1993-1994 for risk factors and reevaluated in 2001-2002. The main outcome measures were CAC and AC, measured by electron beam tomography. Women with PCOS had a higher prevalence of CAC (45.9% vs. 30.6%) and AC (68.9% vs. 55.3%) than controls. After adjustment for age and body mass index, PCOS was a significant predictor of CAC (odds ratio = 2.31; P = 0.049). PCOS subjects were also 4.4 times more likely to meet the criteria for MCS than controls. High-density lipoprotein cholesterol and insulin appeared to mediate the PCOS influence on CAC. Interestingly, total testosterone was an independent risk factor for AC in all subjects after controlling for PCOS, age, and body mass index (P = 0.034). We conclude that women with PCOS are at increased risk of MCS and demonstrate increased CAC and AC compared with controls. Components of MCS mediate the association between PCOS and CAC, independently of obesity.

[Evaluation of effectiveness of Catalin eyedrops in patients with presenile and senile cataract]. / Ocena skutecznosci preparatu Catalin--kropli ocznych u pacjentów z zacma przedstarcza i starcza.

AIM OF THE STUDY: Evaluation of effectiveness of Catalin eye drops in inhibition of cataract or eventual influence on regression of actually present opacities. PATIENTS AND METHOD: 72 patients in age over 40 years with initial cortical cataract and visual acuity better than 0.5 were evaluated. 35 patients were treated with anticataracous drug Catalin, and 37 received placebo. All patients were evaluated with a slit-lamp and modern equipment EAS-1000 (Nidek) before starting research and after 3, 6, 12, 18 and 24 months of treatment. RESULTS: Catalin-eye drops in patients with cortical cataract showed its effectiveness in inhibition of lens opacification and its progression especially in group of patients in age up to 59 years. The increase of lens opacification in this group was only 1.425% (Catalin), and in older group (placebo) even 9.228%. Appropriate, raising effect of the drug can be observed after 18 months of treatment. Catalin-eye drops did not cause any complications during the study. CONCLUSIONS: 1. Catalin-eye drops used in patients with senile and presenile cortical cataract is effective drug in inhibiting lens opacification. 2. The function of the drug is more obvious in group of younger patients (up to 59 years of age) in comparison with older ones. 3. Appropriate, raising effect of the drug can be observed after 18 months of treatment. 4. Catalin-eye drops is well tolerated by the patients even after prolonged application.

Early biochemical characterization of soft-tissue trauma and fracture trauma.

OBJECTIVE: The long-term outcome of trauma patients basically depends on the relation between the clearance capacity of the organism, e.g., the lungs, and the antigenic (inflammatory) load in relation to the amount of damaged and perfused tissue. It is necessary to determine quality and quantity of fracture and soft-tissue damage by clinical means as early as possible. It is unknown whether biochemical markers and the impact of soft-tissue trauma correlate and whether there is a predictive value on clinical outcome. METHODS: A total of 107 trauma patients were prospectively enrolled in the study. Blood samples were collected immediately at the site of accident, at hospital admission, and every 2 hours for an interval of 24 hours, then daily. In addition to the biochemical analysis of 20 different substances, the following data were collected and correlated to the laboratory results: Injury Severity Score, polytrauma score of Hannover, modified fracture index, and soft-tissue index. These primary clinical findings as well as the laboratory data were correlated to criteria of clinical outcome such as length of stay in the intensive care unit, length of hospital stay, infections, systemic inflammatory response syndrome, sepsis, multiple organ failure score according to Goris, and finally to primary (< 72 hours), secondary (> 72 hours), and overall lethality. The determination of individual extent and severity of soft-tissue trauma is based on standard partial body volumes derived from healthy volunteers. In addition, clinical estimation of the degree of soft-tissue damage according to the usual classifications was performed. RESULTS: Significant (p > 0.05) correlations were found between fracture as well as soft-tissue trauma and intensive care unit stay, hospital stay, infections, systemic inflammatory response syndrome, multiple organ failure score, serum concentrations/activities of serum interleukin-6 and -8 and creatine kinase during the first 24 hours after trauma. Severe soft-tissue trauma was related to secondary lethality, however, without statistical significance. CONCLUSION: The amount of fracture and soft-tissue damage can be estimated early by analysis of serum interleukin-6 and creatine kinase and is of great importance with regard to long-term outcome after trauma.

Staphylococcal food poisoning caused by imported canned mushrooms.

From February through April 1989, four outbreaks of staphylococcal food poisoning in the United States were associated with eating mushrooms canned in the People's Republic of China (PRC). In the four outbreaks, 99 persons who ate at a suspect facility developed gastrointestinal symptoms within 24 h, including 18 who were hospitalized. Illness was associated with eating mushrooms at a university cafeteria (relative risk [RR] = 53.0), a hospital cafeteria (RR = 13.8), a pizzeria (odds ratio [OR] = infinity), and a restaurant (OR = infinity) (all P < .0001). Staphylococcal enterotoxin A was found by ELISA in mushrooms at the sites of two outbreaks and in unopened cans from the three plants thought to have produced mushrooms implicated in outbreaks. These investigations led to multistate recalls and a US Food and Drug Administration order to restrict entry into the United States of all mushrooms produced in the PRC; until this action, the United States imported approximately 50 million pounds yearly.

The effect of adjuvant arthritis on the subsequent local inflammatory response in rats.

An assessment was made of the cellular inflammatory response to the subcutaneous implantation of sterile nitrocellulose discs and polyvinyl sponges in both normal rats and rats with adjuvant-induced arthritis. It was found that from 3 days after adjuvant injection the treated animals exhibited a reduced accumulation of inflammatory cells onto the nitrocellulose discs and that this impairment in response was not apparent until the discs had been retained for longer than 24 h. When discs were implanted after non-arthritogenic doses of adjuvant constituents or injection of brewer's yeast no effect was seen on the subsequent response. When polyvinyl sponges were used in adjuvant-treated animals a similar initial reduction in cellular accumulation was observed, which was later followed by increased cell numbers associated with enhanced granuloma formation. Differential cell counts revealed that both neutrophil and mononuclear cell types were affected. Some of the possible mechanisms involved in these observations are discussed.