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.

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Single-Electron Detection and Spectroscopy via Relativistic Cyclotron Radiation.

It has been understood since 1897 that accelerating charges must emit electromagnetic radiation. Although first derived in 1904, cyclotron radiation from a single electron orbiting in a magnetic field has never been observed directly. We demonstrate single-electron detection in a novel radio-frequency spectrometer. The relativistic shift in the cyclotron frequency permits a precise electron energy measurement. Precise beta electron spectroscopy from gaseous radiation sources is a key technique in modern efforts to measure the neutrino mass via the tritium decay end point, and this work demonstrates a fundamentally new approach to precision beta spectroscopy for future neutrino mass experiments.

Dielectric spectroscopy for monitoring human pancreatic islet differentiation within cell-seeded scaffolds in a perfusion bioreactor system.

The long-term in vitro culture and differentiation of human pancreatic islets is still hindered by the inability to emulate a suitable microenvironment mimicking physiological extracellular matrix (ECM) support and nutrient/oxygen perfusion. This is further amplified by the current lack of a non-invasive and rapid monitoring system to readily evaluate cellular processes. In this study, we realized a viable method for non-invasively monitoring isolated human pancreatic islets in vitro. Islets are induced to dedifferentiate into proliferative duct-like structures (DLS) in preparation for potential and subsequent re-differentiation into functional islet-like structures (ILS) in a process reminiscent of islet regeneration strategies. This long-term in vitro process is conducted within a three-dimensional microenvironment involving islets embedded in an optimized ECM gel supported by microfabricated three-dimensional scaffolds. The islet-scaffold is then housed and continuously perfused within chambers of a bioreactor platform. The process in its entirety is monitored through dielectric spectroscopy measurements, yielding an accurate representation of cellular morphology, functionality, and volume fraction. This non-invasive and real-time monitoring tool can be further manipulated to elucidate important information about the optimized cellular microenvironment required for maintaining long-term culture and achieve efficient differentiation for islet regeneration.

The Relationship between Puberty and Risk Taking in the Real World and in the Laboratory.

Adolescence is marked by the emergence and escalation of risk taking. Puberty has been long-implicated as constituting vulnerability for risk behavior during this developmental period. Sole reliance on self-reports of risk taking however poses limitations to understanding this complex relationship. There exist potential advantages of complementing self-reports by using the BART-Y laboratory task, a well-validated measure of adolescent risk taking. Toward this end, we examined the association between self-reported puberty and both self-reported and BART-Y risk taking in 231 adolescents. Results showed that pubertal status predicted risk taking using both methodologies above and beyond relevant demographic characteristics. Advantages of a multimodal assessment toward understanding the effects of puberty in adolescent risk taking are discussed and future research directions offered.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

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.

Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis.

Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms. Genome-wide association studies in European populations have reported significant associations between sarcoidosis and single-nucleotide polymorphisms (SNPs) located in the intergenic region between the C10ORF67 and OTUD1 genes on chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine-mapping at 10p12 and 10q22 to assess associations of genetic variants in these regions with sarcoidosis risk in African-American women, based on 486 sarcoidosis cases and 943 age- and geography-matched controls in a nested case-control study within the Black Women's Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67-OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). Both SNPs are located inside an ∼300 kb low recombination region of chromosome 10p12, suggesting that both SNPs are tagging the same causal variant. Our top SNP (rs11013452) is located inside a smaller linkage disequilibrium block in HapMap YRI, further narrowing the position of the causal SNP to a region of ~8 kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis.

Hypertension and risk of uterine leiomyomata in US black women.

BACKGROUND: Previous studies have found a positive association between hypertension and risk of hysterectomy-confirmed uterine leiomyomata (UL). The association of hypertension with UL confirmed by ultrasound or other surgery is less clear. METHODS: The present study evaluated the association of hypertension with UL incidence according to confirmation method (hysterectomy, other surgery or ultrasound) in the Black Women's Health Study, 1997-2007. We collected prospective data every 2 years on physician-diagnosed hypertension and UL in 22 530 premenopausal women. Validation sub-studies confirmed 99 and 96% of hypertension and UL self-reported diagnoses, respectively. Cox regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association of hypertension and UL, adjusting for potential confounders. RESULTS: During 172 162 person-years of follow-up, there were 6447 incident cases of UL confirmed by ultrasound (n = 5111), hysterectomy (n = 670) or other surgery (n = 666). Treated hypertension was associated with UL confirmed by hysterectomy (IRR = 1.32, 95% CI: 1.06, 1.63), but it was not associated with UL confirmed by ultrasound (IRR = 1.05, 95% CI: 0.96, 1.16) or other surgery (IRR = 1.13, 95% CI: 0.88, 1.46). CONCLUSIONS: Treated hypertension was associated with UL confirmed by hysterectomy, but not UL confirmed by other methods (other surgery or ultrasound). These data suggest it is premature to conclude that hypertension is related to an increased risk of UL. Additional studies are needed to assess whether the association with hysterectomy-confirmed UL can be explained by other sources of bias, such as patient or physician preferences for specific types of medical care.

Perceived environmental restrictions for the participation of children with mild developmental disabilities.

AIM: In light of the International Classification of Functioning, and Health (ICF) model, to assess whether parents of children with mild developmental disabilities perceived various environmental factors as barriers to their child's participation, and whether these factors have a unique contribution to the total explained variance of participation, beyond personal factors. METHODS: Seventy-nine kindergarten children (mean age 5.20 ± 0.52 years old) with mild developmental disabilities and their parents participated in the study. Three questionnaires measuring the child's participation, performance skills and environmental factors were completed by the parents. RESULTS: Parents perceived environmental factors as slightly restricting to their child's participation. Associations were found between home and education factors and the dimensions of child participation - independence, enjoyment and parental satisfaction. Although parents perceived human environmental factors as more restricting than physical factors at home, regression analysis revealed that the latter was found to affect the child participation dimension of independence beyond the contribution of personal factors. INTERPRETATION: These findings are the first, to our knowledge, to support the contribution of environmental factors to the participation of young children with mild developmental disabilities. The results show that environmental factors have significant slight contribution to child's independence in participation beyond other predictors (i.e. personal factors). Therefore, it is recommended to include environmental restrictions measurement in the child evaluation process to facilitate effective intervention programs.

Personal and environmental pathways to participation in young children with and without mild motor disabilities.

OBJECTIVE: Participation in everyday activities has a positive influence upon health and well-being and is considered as an outcome measure. According to recent models child participation is the product of the dynamic interaction between health states and both individual and environmental factors. Children with mild developmental disabilities often present decreased participation in everyday activities. The purpose of this study was to explore the extent to which individual and environmental factors explain the participation of young children, with and without mild motor disabilities. METHODS: The study population included 58 kindergarten children together with their parents (29 children with mild motor disabilities who were referred to occupational therapy and 29 children without motor disabilities). Both groups of children were matched for: age; gender; age of parents; and socio-economic status (SES). We assessed participation using the Child Participation Questionnaire (intensity, diversity, independence, child enjoyment and parental satisfaction) and we assessed children's self-efficacy and motor abilities for individual factors. Parental self-efficacy and SES were collected by questionnaires. RESULTS: Participation diversity (number of activities) was predicted by child and mother self-efficacy and by SES. Child independence and enjoyment as well as parental satisfaction were predicted by child motor ability but mainly by maternal self-efficacy. Results suggest that the total explained variance is more than double when the environmental variables (parental self-efficacy and SES) are inserted to the participation model. CONCLUSIONS: Maternal self-efficacy and SES serve as facilitators to increased participation and well-being of children with mild motor disabilities.

Co-encapsulation of bioengineered IGF-II-producing cells and pancreatic islets: effect on beta-cell survival.

Insulin-like growth factor-II (IGF-II) has been shown to promote pancreatic ß-cell survival. We evaluated the effect of co-encapsulating islets and bioengineered IGF-II-producing cells on islet cell survival. IGF-II or green fast protein (GFP) genes were transferred into TM4 cells, and purified using a neomycin resistance gene, leading to pure cell cultures (TM4-IGF-II or TM4-GFP) with a stable overexpression of the transferred gene. Islets were co-encapsulated with TM4-IGF-II or TM4-GFP, or encapsulated alone in alginate microcapsules. Rat and mouse islet cell survival was studied in vitro and in vivo, respectively. After 12 days in culture, islet viability (dual staining, acridine orange/propidium iodide) was 83% with TM4-IGF-II, compared with 51% (P<0.05) and 41% (P<0.001) with TM4-GFP and islets alone, respectively. The study of islet necrotic centers and the evaluation of islet function, using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, yielded similar results. From 125 days after transplantation, more diabetic mice maintained normoglycemia when they were transplanted with islets co-encapsulated with TM4-IGF-II (4/7). A significant difference for the maintenance of normoglycemia was observed between recipients of islets co-encapsulated with TM4-IGF-II versus islets alone (P=0.023), or with TM4-GFP (P=0.048). In conclusion, the co-encapsulation of islets with bioengineered IGF-II-producing cells promotes islet cell survival.

Can personal and environmental factors explain dimensions of child participation?

OBJECTIVE: One of the main goals of paediatric occupational therapists and other health professionals is to enhance child participation in age-related activities within their communities. According to theoretical models, the act of participation has numerous dimensions, affected by personal and environmental factors. However, there have been relatively few studies undertaken to validate this theory. The purpose of this study was to explore the extent to which personal and environmental factors explain each of five distinct dimensions of child participation, which are: diversity, intensity, independence, enjoyment and subsequent parental satisfaction. METHOD: A convenient sample of 70 kindergarten children without developmental disabilities together with their parents participated in the study. Data were collected using standardized assessments for personal factors and questionnaires for environmental factors. RESULTS: The findings confirmed our hypothesis and revealed that with typical children, motor and cognitive abilities affect participation diversity. Moreover, performance skills and self-perceptions of competence affect their independence levels, while environmental factors contribute to frequency of participation and parental satisfaction. However, these factors on their own do not fully explain the degree of enjoyment experienced by children. CONCLUSIONS: The findings highlight the importance of measuring the full range of participation dimensions, and provide empirical evidence about the nature of child participation. Further studies are warranted to validate this approach for children with developmental difficulties.

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 role of complement in resistance to endogenous and exogenous infection with a common mouse pathogen, Corynebacterium kutscheri.

In mice, the presence or absence of a single complement (C') component, called hc(1), is controlled by two alleles at the Hc locus. The sera of mice which lack this C' component do not manifest C'-mediated immune hemolysis. When challenged with the common mouse pathogen, Corynebacterium kutscheri, mice possessing hemolytic C' fare slightly better than C'-deficient mice. When mice harboring latent C. kutscheri are administered hydrocortisone, which depresses mouse serum C' levels, pseudotuberculosis is activated with equal frequency in mice of both C' types. These data suggest that in at least one situation the presence of the complete hemolytic C' system may be advantageous to the mouse. In contrast, evidence is presented which shows that under normal laboratory conditions, C'-deficient B10.D2 "old line" mice (Hc(0)/Hc(0)) have a survival advantage over C'-positive B10.D2 "new line" mice (Hc(1)/Hic(1)) during the first 3 wk of life. It is therefore concluded that mouse hemolytic C' has a balanced survival value-that is, under one set of conditions it may be advantageous, whereas in another situation, it may be disadvantageous.