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.

Final Result of the Majorana Demonstrator's Search for Neutrinoless Double-ß Decay in

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Erratum: Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator [Phys. Rev. Lett. 129, 080401 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.080401.

Earth Systems to Anthropocene Systems: An Evolutionary, System-of-Systems, Convergence Paradigm for Interdependent Societal Challenges.

Humans have made profound changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change and impacts, renewable energy, adaptive infrastructure, disasters, pandemics, food insecurity, and biodiversity loss) are complex and systemic, with causes, interactions, and consequences that cascade across a globally connected system of systems. In this Critical Review, we turn to our "origin story" for insight, briefly tracing the formation of the Universe and the Earth, the emergence of life, the evolution of multicellular organisms, mammals, primates, and humans, as well as the more recent societal transitions involving agriculture, urbanization, industrialization, and computerization. Focusing on the evolution of the Earth, genetic evolution, the evolution of the brain, and cultural evolution, which includes technological evolution, we identify a nested evolutionary sequence of geophysical, biophysical, sociocultural, and sociotechnical systems, emphasizing the causal mechanisms that first formed, and then transformed, Earth systems into Anthropocene systems. Describing how the Anthropocene systems coevolved, and briefly illustrating how the ensuing societal challenges became tightly integrated across multiple spatial, temporal, and organizational scales, we conclude by proposing an evolutionary, system-of-systems, convergence paradigm for the entire family of interdependent societal challenges of the Anthropocene.

Does land-based exercise-therapy improve physical activity in people with knee osteoarthritis? A systematic review with meta-analyses.

PRIMARY OBJECTIVE: Investigate the effects of land-based exercise-therapy on physical activity in people with knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis of randomised or quasi-randomised trials investigating land-based exercise-therapy on physical activity, fitness, and general health in people with KOA. We updated a 2013 Cochrane review search on exercise-therapy for KOA in April 2021 and applied the Cochrane Risk-of-Bias Tool 1.0 to included articles. Standardised mean differences (SMDs) and 95% confidence intervals (CI) were calculated. GRADE was used to assess certainty of the evidence. RESULTS: Twenty-eight randomised controlled trials (2,789 participants) evaluating the effects of resistance-training (n = 10), walking (n = 6) and mixed-exercise programs (n = 7) were identified. Low to moderate certainty evidence indicated small increases in physical activity for exercise-therapy compared to non-exercise interventions in the short-term (SMD, 95% CI = 0.29, 0.09 to 0.50), but not the medium- (0.03, -0.11 to 0.18) or long-term (-0.06, -0.34 to 0.22). Low certainty evidence indicated large increases in physical activity for walking programs (0.53, 0.11 to 0.95) and mixed-exercise programs (0.67, 0.37 to 0.97) compared to non-exercise interventions in the short-term. Low certainty evidence indicated moderate and small increases in physical activity for resistance-training combined with education focused on pain coping skills and self-efficacy compared to education alone at medium-term follow-up (0.45, 0.19 to 0.71). CONCLUSION: Walking and mixed-exercise, but not resistance-training, may improve physical activity in people with KOA in the short-term. Combining resistance-training with education may increase physical activity in the medium-, but not the long-term, highlighting the potential importance of developing more effective longer-term interventions for people with KOA. Future studies evaluating land-based exercise-therapy are encouraged to include physical activity outcomes and longer-term follow-up to increase the certainty of evidence.

Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator.

The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.

Search for Solar Axions via Axion-Photon Coupling with the Majorana Demonstrator.

Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g_{aγ}<1.45×10^{-9} GeV^{-1} (95% confidence level) for axions with mass up to 100 eV/c^{2}. This improves laboratory-based limits between about 1 eV/c^{2} and 100 eV/c^{2}.

Immediate outcomes following the GLA:D® program in Denmark, Canada and Australia. A longitudinal analysis including 28,370 patients with symptomatic knee or hip osteoarthritis.

OBJECTIVE: To report outcomes across three countries for patients with symptomatic knee or hip OA attending the evidence-based education and exercise therapy program Good Life with osteoArthritis from Denmark (GLA:D®). DESIGN: GLA:D® is a structured treatment program including 2-3 patient education sessions and 12 supervised exercise sessions delivered over 8 weeks by certified health care practitioners. The program was introduced in Denmark in 2013, in Canada 2015 and in Australia 2016. Absolute mean change in pain intensity, number of chair stands in 30 s, 40 m walk test time and Knee injury and Osteoarthritis Outcome Score (KOOS)/Hip dysfunction and Osteoarthritis Outcome Score (HOOS) QOL subscale scores from baseline to immediately after treatment were reported as means and 95 % CIs and proportion of responders for each country. RESULTS: Patients from the three countries improved 26-33% in mean pain intensity, 8-12% in walking speed, 18-30% in chair stand ability and 12-26% in joint-related quality of life from baseline to immediately after treatment, with no clinically relevant differences between patients with hip and knee OA. These improvements correspond with moderate to large within-group effect sizes and 43-47 % of the patients experienced clinically relevant pain reductions. CONCLUSION: About half or more of patients across the three countries were categorized as responders for pain and objective function following the implementation of GLA:D®. These findings indicate positive patient outcomes associated with GLA:D® participation across varying health care systems from implementation of guideline-based patient education and exercise therapy for knee and hip OA.

Postpartum Opioid Use among Military Health System Beneficiaries.

OBJECTIVE: The aim of the study is to evaluate the prevalence and factors associated with opioid prescriptions to postpartum patients among TRICARE beneficiaries receiving care in the civilian health care system versus a military health care facility. STUDY DESIGN: We evaluated postpartum opioid prescriptions filled at discharge among patients insured by TRICARE Prime/Prime Plus using the Military Health System Data Repository between fiscal years 2010 to 2015. We included women aged 15 to 49 years old and excluded abortive pregnancy outcomes and incomplete datasets. The primary outcome investigated mode of delivery and demographics for those filling an opioid prescription. Secondary outcomes compared prevalence of filled opioid prescription at discharge for postpartum patients within civilian care and military care. RESULTS: Of a total of 508,258 postpartum beneficiaries, those in civilian health care were more likely to fill a discharge opioid prescription compared with those in military health care (OR 3.9, 95% CI 3.8-3.99). Cesarean deliveries occurred less frequently in military care (26%) compared with civilian care (30%), and forceps deliveries occurred more frequently in military care (1.38%) compared with civilian care (0.75%). Women identified as Asian race were least likely to fill an opioid prescription postpartum (OR 0.79, 95% CI 0.75-0.83). Women aged 15 to 19 years had a lower odds of filling an opioid prescription (OR 0.83, 95% CI 0.80-0.86). Women associated with a senior officer rank were less likely to fill an opioid prescription postpartum (OR 0.83, 95% CI 0.73-0.91), while those associated with warrant officer rank were more likely to fill an opioid prescription (OR 1.14, 95% CI 1.06-1.23). CONCLUSION: Our data indicates that women who received care in civilian facilities were more likely to fill an opioid prescription at discharge when compared with military facilities. Factors such as race and age were associated with opioid prescription at discharge. This study highlights areas for improvement for potential further studies. KEY POINTS: · Opioid prescription patterns for postpartum women may vary across the country.. · Our study indicates postpartum patients in civilian care are more likely to fill opioids postpartum.. · This study highlights a population which may have an improved opioid prescribing pattern..

Socio-technical scales in socio-environmental modeling: Managing a system-of-systems modeling approach.

System-of-systems approaches for integrated assessments have become prevalent in recent years. Such approaches integrate a variety of models from different disciplines and modeling paradigms to represent a socio-environmental (or social-ecological) system aiming to holistically inform policy and decision-making processes. Central to the system-of-systems approaches is the representation of systems in a multi-tier framework with nested scales. Current modeling paradigms, however, have disciplinary-specific lineage, leading to inconsistencies in the conceptualization and integration of socio-environmental systems. In this paper, a multidisciplinary team of researchers, from engineering, natural and social sciences, have come together to detail socio-technical practices and challenges that arise in the consideration of scale throughout the socio-environmental modeling process. We identify key paths forward, focused on explicit consideration of scale and uncertainty, strengthening interdisciplinary communication, and improvement of the documentation process. We call for a grand vision (and commensurate funding) for holistic system-of-systems research that engages researchers, stakeholders, and policy makers in a multi-tiered process for the co-creation of knowledge and solutions to major socio-environmental problems.

Variations in prenatal screening in a US federal healthcare system: Same coverage, different options.

The Military Health System (MHS) is a federally funded organization that provides care to active duty service members and their beneficiaries. Our objective was to determine what methods of prenatal screening are used by military treatment facilities (MTFs), assess variations between institutions, and determine how practice patterns align with national recommendations. We surveyed all MTFs offering comprehensive prenatal care (n = 49). Departments were asked about aneuploidy screening options, availability of diagnostic testing, and carrier screening. In all, 43 MTFs (88%) completed the survey. Most (39/43) patients were stratified based on risk (predominantly maternal age at delivery and history). The most commonly offered test was combined 1st/2nd trimester screening (59%). Sixty percent routinely offered diagnostic testing, though less than half routinely offered microarrays. The majority offered universal carrier screening for cystic fibrosis (98%) and complete blood count with screening for thalassemias and hemoglobinopathies (88%). At the time of data collection, only five facilities (12%) had implemented spinal muscular atrophy carrier screening. Considerable heterogeneity exists in prenatal aneuploidy testing and carrier screening within the MHS. Standardized guidelines, protocols, and laboratory support would improve processes across the system. Additional resources including genetic counseling support and provider education are needed.

Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention.

PURPOSE OF REVIEW: The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events. RECENT FINDINGS: Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation. There have also been enhancements in understanding of what may contribute to the more severe, hyperhaemolytic nature of DHTRs in SCD, including data regarding 'suicidal red blood cell death' and immune dysregulation amongst transfusion recipients with SCD. With growing recognition and study of hyperhaemolytic DHTRs, there have been improvements in management strategies for this entity, including a multitude of reports on using novel immunosuppressive agents for preventing or treating such reactions. SUMMARY: Delayed serologic and haemolytic reactions remain important and highly relevant transfusion-associated adverse events. Future directions include further unravelling the basic mechanisms, which underlie DHTRs and developing evidence-based approaches for treating these reactions. Implementing practical preventive strategies is also a priority.

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.

Search for Neutrinoless Double-ß Decay in

The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-ß decay in ^{76}Ge. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in ^{76}Ge) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2.5 keV FWHM at Q_{ßß} and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×10^{25} yr (90% C.L.). This result constrains the effective Majorana neutrino mass to below 240-520 meV, depending on the matrix elements used. In our experimental configuration with the lowest background, the background is 4.0_{-2.5}^{+3.1} counts/(FWHM t yr).

An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

BACKGROUND: Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirror that of humans. METHODS: We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of antitumour IgE antibodies. RESULTS: In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a "cytokine storm" or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated antitumour and antiparasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. CONCLUSION: Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena.

Pediatric Oral Motor Feeding Assessments: A Systematic Review.

AIM: To describe the clinical properties and psychometric soundness of pediatric oral motor feeding assessments. METHODS: A systematic search was conducted using Medline, CINAHL, EMBASE, PsycInfo, and HAPI databases. Assessments were analyzed for their clinical and psychometric characteristics. RESULTS: 12 assessment tools were identified to meet the inclusion/exclusion criteria. Clinical properties varied from assessments evaluating oral-motor deficits, screening to identify feeding problems, and monitoring feeding progress. Most assessments were designed for children with developmental disabilities or cerebral palsy. Eleven assessments had psychometric evidence, of these nine had reliability and validity testing (Ability for Basic Feeding and Swallowing Scale for Children, Behavioral Assessment Scale of Oral Functions in Feeding, Dysphagia Disorder Survey, Functional Feeding Assessment-modified, Gisel Video Assessment, Montreal Children's Hospital Feeding Scale, Oral Motor Assessment Scale, Schedule for Oral Motor Assessment, and Screening Tool of Feeding Problems Applied to Children). The Brief Assessment of Motor Function-Oral Motor Deglutition and the Pediatric Assessment Scale for Severe Feeding Problems had reliability testing only. The Slurp Test was not tested for any psychometric properties. Overall, psychometric evidence was inconsistent and inadequate for the evaluative tools.

Running retraining to treat lower limb injuries: a mixed-methods study of current evidence synthesised with expert opinion.

IMPORTANCE: Running-related injuries are highly prevalent. OBJECTIVE: Synthesise published evidence with international expert opinion on the use of running retraining when treating lower limb injuries. DESIGN: Mixed methods. METHODS: A systematic review of clinical and biomechanical findings related to running retraining interventions were synthesised and combined with semistructured interviews with 16 international experts covering clinical reasoning related to the implementation of running retraining. RESULTS: Limited evidence supports the effectiveness of transition from rearfoot to forefoot or midfoot strike and increase step rate or altering proximal mechanics in individuals with anterior exertional lower leg pain; and visual and verbal feedback to reduce hip adduction in females with patellofemoral pain. Despite the paucity of clinical evidence, experts recommended running retraining for: iliotibial band syndrome; plantar fasciopathy (fasciitis); Achilles, patellar, proximal hamstring and gluteal tendinopathy; calf pain; and medial tibial stress syndrome. Tailoring approaches to each injury and individual was recommended to optimise outcomes. Substantial evidence exists for the immediate biomechanical effects of running retraining interventions (46 studies), including evaluation of step rate and strike pattern manipulation, strategies to alter proximal kinematics and cues to reduce impact loading variables. SUMMARY AND RELEVANCE: Our synthesis of published evidence related to clinical outcomes and biomechanical effects with expert opinion indicates running retraining warrants consideration in the treatment of lower limb injuries in clinical practice.