Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Implementation of initiatives designed to improve healthcare worker health and wellbeing during the COVID-19 pandemic: comparative case studies from 13 healthcare provider organisations globally.

BACKGROUND: Healthcare workers are at a disproportionate risk of contracting COVID-19. The physical and mental repercussions of such risk have an impact on the wellbeing of healthcare workers around the world. Healthcare workers are the foundation of all well-functioning health systems capable of responding to the ongoing pandemic; initiatives to address and reduce such risk are critical. Since the onset of the pandemic healthcare organizations have embarked on the implementation of a range of initiatives designed to improve healthcare worker health and wellbeing. METHODS: Through a qualitative collective case study approach where participants responded to a longform survey, the facilitators, and barriers to implementing such initiatives were explored, offering global insights into the challenges faced at the organizational level. 13 healthcare organizations were surveyed across 13 countries. Of these 13 participants, 5 subsequently provided missing information through longform interviews or written clarifications. RESULTS: 13 case studies were received from healthcare provider organizations. Mental health initiatives were the most commonly described health and wellbeing initiatives among respondents. Physical health and health and safety focused initiatives, such as the adaption of workspaces, were also described. Strong institutional level direction, including engaged leadership, and the input, feedback, and engagement of frontline staff were the two main facilitators in implementing initiatives. The most common barrier was HCWs' fear of contracting COVID-19 / fear of passing COVID-19 to family members. In organizations who discussed infection prevention and control initiatives, inadequate personal protective equipment and supply chain disruption were highlighted by respondents. CONCLUSIONS: Common themes emerge globally in exploring the enablers and barriers to implementing initiatives to improve healthcare workers health and wellbeing through the COVID-19 pandemic. Consideration of the themes outlined in the paper by healthcare organizations could help influence the design and deployment of future initiatives ahead of implementation.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

Design of a 3000-Pixel Transition-Edge Sensor X-Ray Spectrometer for Microcircuit Tomography.

Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of ∼ 1 µm. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed.

Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists.

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

Modal instabilities in high power fiber laser oscillators.

Transverse mode competition and instabilities in high-power fiber oscillators have been studied experimentally by monitoring the dynamic power exchanges and characteristic frequencies of the transmitted fundamental mode (FM) and scattered high-order modes (HOMs) of the fiber laser cavity under CW and pulsed pumping. The FM and HOM power evolution indicates the presence of two competing effective laser cavities which result in rich output dynamics and full chaotic operation. The thermal and inversion related contributions to the observed instabilities have been identified by monitoring the associated characteristic instability frequencies under pulsed pumping. It is shown that in the transient regime, both inversion and thermal effects contribute successively to the observed power instabilities. Increasing the pump power leads to full chaotic response through an interplay between transverse and longitudinal mode instabilities.

A transition-edge sensor-based x-ray spectrometer for the study of highly charged ions at the National Institute of Standards and Technology electron beam ion trap.

We report on the design, commissioning, and initial measurements of a Transition-Edge Sensor (TES) x-ray spectrometer for the Electron Beam Ion Trap (EBIT) at the National Institute of Standards and Technology (NIST). Over the past few decades, the NIST EBIT has produced numerous studies of highly charged ions in diverse fields such as atomic physics, plasma spectroscopy, and laboratory astrophysics. The newly commissioned NIST EBIT TES Spectrometer (NETS) improves the measurement capabilities of the EBIT through a combination of high x-ray collection efficiency and resolving power. NETS utilizes 192 individual TES x-ray microcalorimeters (166/192 yield) to improve upon the collection area by a factor of ∼30 over the 4-pixel neutron transmutation doped germanium-based microcalorimeter spectrometer previously used at the NIST EBIT. The NETS microcalorimeters are optimized for the x-ray energies from roughly 500 eV to 8000 eV and achieve an energy resolution of 3.7 eV-5.0 eV over this range, a more modest (<2×) improvement over the previous microcalorimeters. Beyond this energy range, NETS can operate with various trade-offs, the most significant of which are reduced efficiency at lower energies and being limited to a subset of the pixels at higher energies. As an initial demonstration of the capabilities of NETS, we measured transitions in He-like and H-like O, Ne, and Ar as well as Ni-like W. We detail the energy calibration and data analysis techniques used to transform detector counts into x-ray spectra, a process that will be the basis for analyzing future data.

Factors Associated with Self-Injurious Behaviors in Children with Autism Spectrum Disorder: Findings from Two Large National Samples.

In this study, we explored potential associations among self-injurious behaviors (SIB) and a diverse group of protective and risk factors in children with autism spectrum disorder from two databases: Autism and Developmental Disabilities Monitoring (ADDM) Network and the Autism Speaks-Autism Treatment Network (AS-ATN). The presence of SIB was determined from children's records in ADDM and a parent questionnaire in AS-ATN. We used multiple imputation to account for missing data and a non-linear mixed model with site as a random effect to test for associations. Despite differences between the two databases, similar associations were found; SIB were associated with developmental, behavioral, and somatic factors. Implications of these findings are discussed in relation to possible etiology, future longitudinal studies, and clinical practice.

High-peak-power, high-energy, high-average-power pulsed fiber laser system with versatile pulse duration and shape.

We present a pulsed fiber laser system with average power up to 265 W, pulse energy up to 10.6 mJ, pulse duration adjustable in the range 500 ps-500 ns, repetition rate fully controllable from single-shot operation up to 1 MHz, and the ability to control peak power independently of pulse energy. The system has a compact, all-spliced construction. Such a versatile laser will have wide applications in materials processing.

Lifestyle factors including less cutaneous sun exposure contribute to starkly lower vitamin D levels in U.K. South Asians compared with the white population.

BACKGROUND: Long-standing concerns over the vitamin D status of South Asian adults in the U.K. require studies using statistically valid sample sizes to measure annual variation and contributory lifestyle factors. OBJECTIVES: To measure annual variation in the vitamin D status of U.K. South Asians, to determine the associated lifestyle influences, and to compare these with a similar study of white adults. METHODS: A single-centre, prospective cohort study measuring circulating 25-hydroxyvitamin D [25(OH)D], sunlight exposure levels and lifestyle factors for 1 year in 125 ambulant South Asian adults with sun-reactive skin type V, aged 20-60 years, in Greater Manchester, U.K. (53·5°N). RESULTS: The 25(OH)D levels of South Asians were alarmingly low. In summer, their median 25(OH)D level was 9·0 ng mL(-1) , [interquartile range (IQR) 6·7-13·1], falling to 5·8 ng mL(-1) (IQR 4·0-8·1) in winter. This compared with values in the white population of 26·2 ng mL(-1) (IQR 19·9-31·5) in summer and 18·9 ng mL(-1) IQR (11·6-23·7) in winter. Median daily dietary vitamin D was lower in South Asians (1·32 µg vs. 3·26 µg for white subjects) and was compounded by low supplement use. Despite similar times spent outdoors, ultraviolet (UV) dosimeters recorded lower personal UV exposure among South Asians, indicating sun avoidance when outside, while sun exposure diaries recorded lower amounts of skin surface exposure. CONCLUSIONS: The majority of South Asians never reached sufficiency in vitamin D status. Lifestyle differences, with lower oral intake, sun exposure and rates of cutaneous production due to darker skin, indicate that standard advice on obtaining sufficient vitamin D needs modification for the South Asian community in the U.K.

The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population.

BACKGROUND: Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25-hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL⁻¹) is an appropriate and feasible target at population level. OBJECTIVES: We examined whether personal sunlight exposure levels can provide vitamin D sufficient (≥ 20 ng mL⁻¹) and optimal status in the U.K. public. METHODS: This prospective cohort study measured circulating 25(OH)D monthly for 12 months in 125 white adults aged 20-60 years in Greater Manchester. Dietary vitamin D and personal ultraviolet radiation (UVR) exposure were assessed over 1-2 weeks in each season. The primary analysis determined the post-summer peak 25(OH)D required to maintain sufficiency in wintertime. RESULTS: Dietary vitamin D remained low in all seasons (median 3·27 µg daily, range 2·76-4·15) while personal UVR exposure levels were high in spring and summer, low in autumn and negligible in winter. Mean 25(OH)D levels were highest in September [28·4 ng mL⁻¹; 28% optimal, zero deficient (<5 ng mL⁻¹)], and lowest in February (18·3 ng mL⁻¹; 7% optimal, 5% deficient). A February 25(OH)D level of 20 ng mL⁻¹ was achieved following a mean (95% confidence interval) late summer level of 30·4 (25·6-35·2) and 34·9 (27·9-41·9) ng mL⁻¹ in women and men, respectively, with 62% of variance explained by gender and September levels. CONCLUSIONS: Late summer 25(OH)D levels approximating the optimal range are required to retain sufficiency throughout the U.K. winter. Currently the majority of the population fails to reach this post-summer level and becomes vitamin D insufficient during the winter.

The impact of photosensitivity disorders on aspects of lifestyle.

BACKGROUND: Photosensitivity disorders involve an abnormal skin reaction to sunlight exposure and affect a substantial percentage of the population. No previous studies have directly compared lifestyle attributes between photosensitive and healthy individuals. OBJECTIVES: To assess the impact of photosensitivity on time spent outdoors in the U.K., holiday behaviour, use of sunscreens and vitamin D supplements, and employment status. METHODS: Questionnaires were completed by ambulant photosensitive and healthy adults aged 18-60 years residing in Greater Manchester. RESULTS: Forty-five adults with moderate-severe photosensitivity and 124 healthy adults completed the questionnaire. This revealed that photosensitive subjects spent significantly less time outdoors in the U.K. on both summer weekdays (P < 0·01) and summer weekends (P < 0·0001) than healthy subjects, took fewer holidays per year (P < 0·05), and spent less time outdoors on a sunny holiday (P < 0·0001). They wore clothing that covered a wider skin area (P < 0·0001), and use of sunscreen was greater (both frequency of application and area covered) in the photosensitive group outside of holiday time (P < 0·0001), but not when on a sunny holiday, as healthy people increased their sunscreen use at this time. Despite the reduced sun exposure, photosensitive subjects were no more likely to take vitamin D supplements than healthy subjects were; they also exhibited a significantly higher rate of unemployment (P < 0·05). CONCLUSIONS: Photosensitivity disorders negatively influence lifestyle including employment status; more attention is required to the socioeconomic impact of these conditions.

Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.

Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.

The risks and costs of multiple-generic substitution of topiramate.

OBJECTIVE: To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). METHODS: Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. RESULTS: In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). CONCLUSION: Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Improved detection of Histoplasma antigenemia following dissociation of immune complexes.

The sensitivity for detection of Histoplasma antigen is lower in serum than in urine. In other antigen assays, treatment of serum at 104 degrees C in the presence of EDTA was required for detection of antigenemia. Sensitivity and specificity for detection of Histoplasma antigenemia were examined with or without EDTA heat treatment of the serum using the MVista Histoplasma antigen enzyme immunoassay. A total of 94.6% of serum specimens from patients with AIDS and histoplasmosis that were negative untreated were positive after EDTA-heat treatment. Two-thirds of the negative serum specimens from patients with probable histoplasmosis, based upon clinical suspicion and Histoplasma antigenuria, were positive after heat treatment. Specificity was 99.0% in controls, including healthy subjects and patients in whom histoplasmosis or blastomycosis, were excluded. Precision and reproducibility were good and excellent, respectively. These findings demonstrate improvement in sensitivity without reduction in specificity, precision, or reproducibility after heat-EDTA treatment.

Performance characteristics of the platelia Aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in bronchoalveolar lavage fluid.

We have evaluated the Platelia Aspergillus enzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.