Searching for Heavy Dark Matter near the Planck Mass with XENON1T.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10^{12} and 2×10^{17} GeV/c^{2}. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale.

First Dark Matter Search with Nuclear Recoils from the XENONnT Experiment.

We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03) ton yr exposure used for this search, the intrinsic ^{85}Kr and ^{222}Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3) events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10^{-47} cm^{2} for a WIMP mass of 28 GeV/c^{2} at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure.

Back to the future: breast surgery with tumescent local anesthesia (TLA)?

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.

Search for New Physics in Electronic Recoil Data from XENONnT.

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.

Airborne concentrations and chemical considerations of radioactive ruthenium from an undeclared major nuclear release in 2017.

In October 2017, most European countries reported unique atmospheric detections of aerosol-bound radioruthenium (106Ru). The range of concentrations varied from some tenths of µBq·m-3 to more than 150 mBq·m-3 The widespread detection at such considerable (yet innocuous) levels suggested a considerable release. To compare activity reports of airborne 106Ru with different sampling periods, concentrations were reconstructed based on the most probable plume presence duration at each location. Based on airborne concentration spreading and chemical considerations, it is possible to assume that the release occurred in the Southern Urals region (Russian Federation). The 106Ru age was estimated to be about 2 years. It exhibited highly soluble and less soluble fractions in aqueous media, high radiopurity (lack of concomitant radionuclides), and volatility between 700 and 1,000 °C, thus suggesting a release at an advanced stage in the reprocessing of nuclear fuel. The amount and isotopic characteristics of the radioruthenium release may indicate a context with the production of a large 144Ce source for a neutrino experiment.

[Emergency service care of mountain bike elite races : Rescue concept and analysis of 5 years of world cup elite cross-country/downhill and marathon stage races]. / Rettungsdienstliche Betreuung von Mountainbike-Eliterennen : Rettungskonzept und Analyse von 5 Jahren Worldcup-Elite Cross-Country/Downhill und Marathon-Etappenrennen.

BACKGROUND: Despite the ever-gaining popularity of mountain bike sports, the number of studies in regards to injury patterns and organizational aspects of rescue services is rather sparse. To efficiently support mass events such as the Union Cycliste Internationale (UCI) World Cup and UCI Championship, the World Championships and Swiss Epic Marathon, efficient rescue concepts are crucial. Challenges include high risk of injury in disciplines such as Downhill as well as the need to cover events in remote and often rough terrain in the Swiss Alps during the Swiss Epic Marathon, providing medical services not only for participants but also for spectators. We analysed the number of injuries sustained by participants as well as the different challenges for rescue services at these events. METHODS: Retrospective analysis of emergencies at the Swiss Epic from 2016-2020, the UCI World Cup Races from 2015-2017 and 2019, as well as the UCI Championship 2018. Summary of the organizational aspects of the attending rescue services and special requirements and track concepts used at the events analysed. RESULTS: Significantly higher probability of injury in Downhill disciplines vs. Cross-Country. In particular traumatic brain injury and extremity fractures. More severe injuries (NACA III to IV) were more common in Downhill compared to other disciplines (p < 0,01). CONCLUSION: Mass events require rescue concepts tailored to the competition's sport as well as it's terrain. The number of injuries was low but their severity necessitates highly qualified personnel and efficient rescue logistics to be planned beforehand. GPS-tracking and central disposition of mobile rescue resources is essential for marathon races while track competitions benefit from a mix of stationary posts and mobile units.

The Occupational Participation of Latinx Cancer Survivors and Their Family Caregivers Living in Survivorship: A Qualitative Exploration Informed by Multiple Stakeholders.

The purpose of this study was to examine the lived experiences of Latinx cancer survivors and their family caregivers during survivorship. Eighteen semi-structured interviews were conducted with a variety of stakeholders including Latinx cancer survivors (n = 8), their family caregivers (n = 5), and cancer care providers (n = 5). Data were analyzed thematically to describe occupational participation. Latinx families lived in political, economic, language, and social contexts that facilitated and hindered their well-being. Survivors simultaneously experienced occupational deprivation and posttraumatic growth. To promote occupational justice, occupational therapy practitioners and researchers are called to partner with Latinx survivors and their families to facilitate skills needed for everyday participation.

Triangle Singularity as the Origin of the a_{1}(1420).

The COMPASS Collaboration experiment recently discovered a new isovector resonancelike signal with axial-vector quantum numbers, the a_{1}(1420), decaying to f_{0}(980)π. With a mass too close to and a width smaller than the axial-vector ground state a_{1}(1260), it was immediately interpreted as a new light exotic meson, similar to the X, Y, Z states in the hidden-charm sector. We show that a resonancelike signal fully matching the experimental data is produced by the decay of the a_{1}(1260) resonance into K^{*}(→Kπ)K[over ¯] and subsequent rescattering through a triangle singularity into the coupled f_{0}(980)π channel. The amplitude for this process is calculated using a new approach based on dispersion relations. The triangle-singularity model is fitted to the partial-wave data of the COMPASS experiment. Despite having fewer parameters, this fit shows a slightly better quality than the one using a resonance hypothesis and thus eliminates the need for an additional resonance in order to describe the data. We thereby demonstrate for the first time in the light-meson sector that a resonancelike structure in the experimental data can be described by rescattering through a triangle singularity, providing evidence for a genuine three-body effect.

Timing and climate forcing of volcanic eruptions for the past 2,500 years.

Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi-millennium quantification of climate response to volcanic forcing.

Osseous hydatidosis of the proximal femur: a rare diagnosis in revision total hip arthroplasty.

Musculoskeletal hydatidosis is a rare but severe disease in central Europe. This case report presents the incidental finding of an osseous hydatidosis after cementless revision total hip arthroplasty in a patient without a preoperative history of hydatidosis or any clinical symptoms. Revision total hip arthroplasty had been necessary due to a septic osteonecrosis of the femoral head 2 years after osteosynthesis of a traumatic proximal femur fracture with a sliding hip screw. The positive sample was taken out of the greater trochanter in the area of the possible former entry point for the lag screw, which was macroscopic inconspicuous. Sero-analysis could afterwards confirm the suspected diagnosis. Postoperative chemotherapy with albendazole was performed for 6 months. A full-body MRI did not reveal any further cysts. This case demonstrates a possible impact of migration on the expected pathogens in revision arthroplasty. This demonstrates that in revision arthroplasty, an infection with this parasite also has to be taken into account, if the patients come from an area endemic for hydatidosis.

Scoring Depression on a Common Metric: A Comparison of EAP Estimation, Plausible Value Imputation, and Full Bayesian IRT Modeling.

There are a growing number of item response theory (IRT) studies that calibrate different patient-reported outcome (PRO) measures, such as anxiety, depression, physical function, and pain, on common, instrument-independent metrics. In the case of depression, it has been reported that there are considerable mean score differences when scoring on a common metric from different, previously linked instruments. Ideally, those estimates should be the same. We investigated to what extent those differences are influenced by different scoring methods that take into account several levels of uncertainty, such as measurement error (through plausible value imputation) and item parameter uncertainty (through full Bayesian IRT modeling). Depression estimates from different instruments were more similar, and their corresponding confidence/credible intervals were larger when plausible value imputation or Bayesian modeling was used, compared to the direct use of expected a posteriori (EAP) estimates. Furthermore, we explored the use of Bayesian IRT models to update item parameters based on newly collected data.

[Hepatocellular carcinomas and their mimics]. / Hepatozelluläre Karzinome und leberzellähnliche Tumoren.

High resolution cross-sectional imaging techniques means that even small, well-differentiated hepatocellular tumors can also be diagnosed with biopsy. In cirrhotic liver tissue, macroregenerative and dysplastic nodules must be discriminated from hepatocellular cancer (HCC). In non-cirrhotic liver tissue the differential diagnosis includes hepatocellular adenoma, macroregeneratory nodules, fibrolamellar carcinoma, as well as primary tumors and metastases. The diagnostic procedure includes matrix diagnosis of the tumor-bearing liver tissue, cyto- and histomorphologic analysis including capillarization of vascular bed, and adapted immunohistological testing with antibodies which underline possible malignancy or hepatocellular differentiation. A flow chart for the diagnosis of hepatocellular carcinomas and their mimics on liver biopsies is presented.

Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop.

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.

Potential Source Apportionment and Meteorological Conditions Involved in Airborne 131I Detections in January/February 2017 in Europe.

Traces of particulate radioactive iodine (131I) were detected in the European atmosphere in January/February 2017. Concentrations of this nuclear fission product were very low, ranging 0.1 to 10 µBq m-3 except at one location in western Russia where they reached up to several mBq m-3. Detections have been reported continuously over an 8-week period by about 30 monitoring stations. We examine possible emission source apportionments and rank them considering their expected contribution in terms of orders of magnitude from typical routine releases: radiopharmaceutical production units > sewage sludge incinerators > nuclear power plants > spontaneous fission of uranium in soil. Inverse modeling simulations indicate that the widespread detections of 131I resulted from the combination of multiple source releases. Among them, those from radiopharmaceutical production units remain the most likely. One of them is located in Western Russia and its estimated source term complies with authorized limits. Other existing sources related to 131I use (medical purposes or sewage sludge incineration) can explain detections on a rather local scale. As an enhancing factor, the prevailing wintertime meteorological situations marked by strong temperature inversions led to poor dispersion conditions that resulted in higher concentrations exceeding usual detection limits in use within the informal Ring of Five (Ro5) monitoring network.

An initial psychometric evaluation of the German PROMIS v1.2 Physical Function item bank in patients with a wide range of health conditions.

OBJECTIVES: To translate the PROMIS Physical Function (PF) item bank version 1.2 into German and to investigate psychometric properties of resulting full bank and seven derived short forms. DESIGN: Cross-sectional psychometric study. SETTING: Inpatient and outpatient clinics of the Department of Psychosomatic Medicine at Charité-Universitätsmedizin Berlin, Germany. SUBJECTS: A total of 10 adult patients with various chronic diseases participated in cognitive debriefing interviews. The final item bank was administered to n = 266 adult patients with a broad range of medical conditions. INTERVENTIONS: Patient-reported outcome assessment as part of routine care. MAIN MEASURES: PROMIS v1.2 PF bank; MOS SF-36 PF scale (PF-10). RESULTS: Cross-cultural adaptation of the item bank followed established guidelines. For the final German translation, the corrected item-total correlations ranged from 0.44 to 0.84. Cronbach's alpha was high for each PROMIS PF short form ( α = 0.88-0.96). The full PROMIS PF bank and most short forms correlated highly with the SF-36 PF-10 ( r = 0.85-0.90), with the exception of PROMIS Upper Extremity ( r = 0.64). PROMIS Upper Extremity showed ceiling effects and lower agreement with the full bank than other short forms. Unidimensionality was supported for all PROMIS PF measures using traditional factor analysis and nonparametric item response theory. CONCLUSION: The German PROMIS PF bank was found to be conceptually equivalent to the English version and fulfilled the psychometric requirements for use of short forms in clinical practice. Future studies should pay particular attention to samples with upper extremity functional limitations to further investigate the dimensional structure of PF as conceptualized according to PROMIS.

De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel.

BACKGROUND: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. PATIENTS AND METHODS: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients. RESULTS: From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population. CONCLUSION: Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.

Patterns and Drivers of Costs for Neuroendocrine Tumor Care: A Comparative Population-Based Analysis.

BACKGROUND: Little is known about resource use in the care of neuroendocrine tumors (NETs). This study defined patterns of costs in NET management and compared them with those of a more common malignancy, colon cancer (CC). METHODS: Using a provincial cancer registry (2004-2012), NET patients were identified and matched at a ratio of 1-3 with CC patients. Four phases of care were examined: pre-diagnostic (PreDx: -2 years to -181 days), diagnostic (Dx: -180 days to +180 days), postdiagnostic (PostDx: +181 days to +3 years), and prolonged post-diagnostic (PPostDx: +181 days to +9 years). The mean costs per patient were compared, and cost predictors were analyzed with quintile regression. RESULTS: Of 3827 NETs, 3355 were matched with 9320 CCs. The PreDx mean NET costs were higher than the CC costs ($5877 vs $5368; p = 0.06), driven by nondrug costs. They were lower in the Dx and PostDx phases (both p < 0.01). For PPostDx, the drug costs were higher for NETs ($26,788 vs $7827; p < 0.01), representing 41% of the costs versus 16% of the costs for CC. Older age and comorbidities predicted higher NET costs in all phases. Lower socioeconomic status (SES) predicted higher costs in the initial phases and higher SES costs in the PPost-Dx phase. Gastroenteric NETs were associated with lower costs in the Dx phase [parameter estimate (PE), -$13,644] and pancreatic NETs with higher costs in PostDx phase (PE, $3348). CONCLUSION: Currently, NETs represent a potential important health care burden. The NET cost patterns differed from those for CC, with the highest costs during the PPostDx phase. The SES and primary NET site affected costs differently at different time points. These data can inform resource allocation tailored to the needs for NETs.

What Is the Actual Local Crystalline Structure of Uranium Dioxide, UO2? A New Perspective for the Most Used Nuclear Fuel.

Up to now, uranium dioxide, the most used nuclear fuel, was said to have a Fm3̅m crystalline structure from 30 to 3000 K, and its behavior was modeled under this assumption. However, recently X-ray diffraction experiments provided atomic pair-distribution functions of UO2, in which UO distance was shorter than the expected value for the Fm3̅m space group. Here we show neutron diffraction results that confirm this shorter UO bond, and we also modeled the corresponding pair-distribution function showing that UO2 has a local Pa3̅ symmetry. The existence of a local lower symmetry in UO2 could explain some unexpected properties of UO2 that would justify UO2 modeling to be reassessed. It also deserves more study from an academic point of view because of its good thermoelectric properties that may originate from its particular crystalline structure.

www.common-metrics.org: a web application to estimate scores from different patient-reported outcome measures on a common scale.

BACKGROUND: Recently, a growing number of Item-Response Theory (IRT) models has been published, which allow estimation of a common latent variable from data derived by different Patient Reported Outcomes (PROs). When using data from different PROs, direct estimation of the latent variable has some advantages over the use of sum score conversion tables. It requires substantial proficiency in the field of psychometrics to fit such models using contemporary IRT software. We developed a web application ( http://www.common-metrics.org ), which allows estimation of latent variable scores more easily using IRT models calibrating different measures on instrument independent scales. RESULTS: Currently, the application allows estimation using six different IRT models for Depression, Anxiety, and Physical Function. Based on published item parameters, users of the application can directly estimate latent trait estimates using expected a posteriori (EAP) for sum scores as well as for specific response patterns, Bayes modal (MAP), Weighted likelihood estimation (WLE) and Maximum likelihood (ML) methods and under three different prior distributions. The obtained estimates can be downloaded and analyzed using standard statistical software. CONCLUSIONS: This application enhances the usability of IRT modeling for researchers by allowing comparison of the latent trait estimates over different PROs, such as the Patient Health Questionnaire Depression (PHQ-9) and Anxiety (GAD-7) scales, the Center of Epidemiologic Studies Depression Scale (CES-D), the Beck Depression Inventory (BDI), PROMIS Anxiety and Depression Short Forms and others. Advantages of this approach include comparability of data derived with different measures and tolerance against missing values. The validity of the underlying models needs to be investigated in the future.