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Abstract To design incentives towards achieving climate mitigation targets, it is important to understand the mechanisms that affect individual climate decisions such as solar panel installation. It has been shown that peer effects are important in determining the uptake and spread of household photovoltaic installations. Due to coarse geographical data, it remains unclear whether this effect is generated through geographical proximity or within groups exhibiting similar characteristics. Here we show that geographical proximity is the most important predictor of solar panel implementation, and that peer effects diminish with distance. Using satellite imagery, we build a unique geo-located dataset for the city of Fresno to specify the importance of small distances. Employing machine learning techniques, we find the density of solar panels within the shortest measured radius of an address is the most important factor in determining the likelihood of that address having a solar panel. The importance of geographical proximity decreases with distance following an exponential curve with a decay radius of 210 meters. The dependence is slightly more pronounced in low-income groups. These findings support the model of distance-related social diffusion, and suggest priority should be given to seeding panels in areas where few exist.

Abstract The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the $$^{222}$$ 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a $$^{222}$$ 222 Rn activity concentration of $$10\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ 10 μ Bq / kg in $$3.2\,\mathrm{t}$$ 3.2 t of xenon. The knowledge of the distribution of the $$^{222}$$ 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the $$^{222}$$ 222 Rn activity concentration in XENON1T. The final $$^{222}$$ 222 Rn activity concentration of $$(4.5\pm 0.1)\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ ( 4.5 ± 0.1 ) μ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment.

Abstract Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

Abstract Background Although medical ethics is an indispensable part of dental education, it has not played a relevant role in the dental curriculum thus far. This study is aimed at developing and validating a questionnaire that identifies semester-specific ethical issues, in order to develop longitudinal ethic modules. Methods March 2018 a workshop on item generation was coordinated, using Delphi method; followed by a cognitive testing with students (2nd, 4th, 10th semesters, n = 12). A pilot test was carried out with students from different semesters (n = 60). The distribution of response frequencies and missing values were determined. The questionnaire used for validation consisted of three dimensions: ethical knowledge, dealing with ethical issues, expectations in terms of teaching. The psychometric examination was carried out by preclinical students (n = 105) and clinical semesters (n = 110) January 2019. Results After cognitive testing and piloting, some items were reformulated, so that a questionnaire with 127 items was used for validation. The individual dimensions were assigned to various factors with excellent to acceptable internal consistency (Cronbach’s α 0.72–0.96). Conclusion The questionnaire has an acceptable to excellent consistency and suggests that the different dimensions are conclusive. With this questionnaire, ethical issues in dentistry can be mapped and teaching contents identified.

PurposeTo compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery.MethodsSixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%.ResultsThe Median follow-up was 4.93 (0.57–8.65) years for R-HF and 5.02 (0.65–8.72) years for L-NF (p=0.236). The median age was 68 (60–83 and 60–80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273–2805) cm3 (R-HF) and 1058.28 (315–2709) cm3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found.ConclusionIn this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT.

Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond. Herein we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors. Retention of the normal BRCA1 or BRCA2 allele (absence of locus-specific loss of heterozygosity (LOH)) is observed in 7% of BRCA1 ovarian, 16% of BRCA2 ovarian, 10% of BRCA1 breast, and 46% of BRCA2 breast tumors. These tumors have equivalent homologous recombination deficiency scores to sporadic tumors, significantly lower than scores in tumors with locus-specific LOH (ovarian, P = 0.0004; breast P

Abstract We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, $$^7$$ 7 Be, $$^{13}$$ 13 N, $$^{15}$$ 15 O and pep. The precision of the $$^{13}$$ 13 N, $$^{15}$$ 15 O and pep components is hindered by the double-beta decay of $$^{136}$$ 136 Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, $$\sin ^2\theta _w$$ sin 2 θ w , and the electron-type neutrino survival probability, $$P_{ee}$$ P ee , in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and $$^7$$ 7 Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1–2.5 $$\sigma $$ σ significance, independent of external measurements from other experiments or a measurement of $$^8$$ 8 B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of $$^{131}$$ 131 Xe.

Abstract Introduction The spine represents the site which is most frequently affected by bone metastases in patients with systemic cancer. Of all local treatment options, combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provides both, instantaneous stabilization and immediate pain relief. We here report on the long-term outcomes of the largest cohort treated with Kypho-IORT to date. Methods Between 2009 and 2019 a total of 104 patients underwent Kypho-IORT to vertebral tumors in the thoracic, lumbar, or sacral spine with transpedicular kyphoplasty and intraoperative irradiation with a needle-shaped electronic brachytherapy source at our center. Patients were treated either on trial, within the prospective Kypho-IORT studies (NCT01280032 and NCT02773966), or, after completion of the study, off trial but compliant with the study protocol. Follow-up and imaging with computed tomography (CT) or magnetic resonance imaging was scheduled after 3 and 6 months and then bi-annually. Results A total of 143 vertebrae (89 thoracic spine, 53 lumbar spine, and 1 sacral spine) were treated in 104 patients. The median follow-up was 14.5 months (range 0.4–109). Local progression occurred in 10 patients (10 vertebrae) after a median time of 22.3 months (range 1.5–73) resulting in local control rates of 97.1, 95.9, and 94.2% at 6, 12, and 24 months, respectively. Overall survival was 74.6, 61.7, and 50.3% at 6, 12, and 24 months, respectively. A single serious adverse event was reported. Conclusion In addition to immediate pain reduction and stabilization, Kypho-IORT shows excellent long-term local control with minimal side effects.

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov ; NCT04375605 ; Registered 4th May 2020;

Abstract Xenon dual-phase time projection chambers designed to search for weakly interacting massive particles have so far shown a relative energy resolution which degrades with energy above $$\sim $$ ∼ 200 keV due to the saturation effects. This has limited their sensitivity in the search for rare events like the neutrinoless double-beta decay of $$^{136} \hbox {Xe}$$ 136Xe at its Q value, $$Q_{\beta \beta }\simeq 2.46\,\hbox {MeV}$$ Qββ≃2.46MeV . For the XENON1T dual-phase time projection chamber, we demonstrate that the relative energy resolution at $$1\,\sigma /\mu $$ 1σ/μ is as low as ($$0.80 \pm 0.02$$ 0.80±0.02 ) % in its one-ton fiducial mass, and for single-site interactions at $$Q_{\beta \beta }$$ Qββ . We also present a new signal correction method to rectify the saturation effects of the signal readout system, resulting in more accurate position reconstruction and indirectly improving the energy resolution. The very good result achieved in XENON1T opens up new windows for the xenon dual-phase dark matter detectors to simultaneously search for other rare events.

The computational effort for wind turbine design load calculations is more extreme than it is for other applications (e.g., aerospace), which necessitates the use of efficient but low-fidelity models. Traditionally the blade element momentum (BEM) method is used to resolve the rotor aerodynamic loads for this purpose, as this method is fast and robust. With the current trend of increasing rotor size, and consequently large and flexible blades, a need has risen for a more accurate prediction of rotor aerodynamics. Previous work has demonstrated large improvement potential in terms of fatigue load predictions using vortex wake models together with a manageable penalty in computational effort. The present publication has contributed towards making vortex wake models ready for application to certification load calculations. The observed reduction in flapwise blade root moment fatigue loading using vortex wake models instead of the blade element momentum (BEM) method from previous publications has been verified using computational fluid dynamics (CFD) simulations. A validation effort against a long-term field measurement campaign featuring 2.5 MW turbines has also confirmed the improved prediction of unsteady load characteristics by vortex wake models against BEM-based models in terms of fatigue loading. New light has been shed on the cause for the observed differences and several model improvements have been developed, both to reduce the computational effort of vortex wake simulations and to make BEM models more accurate. Scoping analyses for an entire fatigue load set have revealed the overall fatigue reduction may be up to 5 % for the AVATAR 10 MW rotor using a vortex wake rather than a BEM-based code.

Abstract Background Soft tissue sarcomas (STS) treatment remains a therapeutic challenge. Intraoperative radiotherapy (IORT) resembles a safe and efficient for STS treatment. The first data on electronic-IORT (eIORT) using low-energy photons is herein presented. Methods Thirty-one patients with newly and recurrent STS were retrospectively assessed. EIORT was applied with low-energy photons during surgery. The dose was either prescribed to the applicator surface (spherical applicators) or 5 mm depth (flat applicators). Overall progression-free survival (O-PFS), local progression-free survival (L-PFS), overall survival (OS) and adverse events were evaluated. Results Median follow-up was 4.88 (1.0–8.95) years. Twenty-five patients (80.6%) had recurrent STS with prior treatment. The resection status was R1 in 25.8% and R2 in 6.5%. The distribution was 51.7% for extremities, 35.5% for abdomen and pelvis, 9.7% for thorax and 3.2% for head and neck tumors. The median O-PFS was 11.0 months, with 42.6% 5-year estimated O-PFS. The only local recurrence in the primary setting occurred after 22 months. Median L-PFS in recurrent STS was 12.5 months, with 65.5% 5-year estimated L-PFS. The 5-year OS estimated rate was 94.7% (3 events after 7 years). No G3 toxicity related to eIORT was observed. Two patients exhibited G2 acute neuropathic pain. Late neuropathic pain was seen in 6 patients being 3 graded as G1 and 3 as G2. No wound-related toxicity was found. Conclusion Electronic IORT with low-energy photons is a safe treatment option for STS, yielding similar outcomes as historical series reporting IORT with electrons or HDR brachytherapy.

Abstract Background With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection. Case presentation A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death. Conclusion Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered.

PurposeThe purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort.Materials/MethodsPatients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors.ResultsA total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12–180) months, and age was 58 (27–86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6–20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age

As carbon emissions continue to grow, removing carbon dioxide (CO2) from the atmosphere will be necessary to curb the impact of climate change, with the need to remove over a billion tons of CO2 in the next decade. Direct air capture (DAC) is a promising technology for removing atmospheric carbon dioxide, with a handful of systems deployed around the globe. As currently deployed, however, tens of millions of these systems are needed to address current and historic emissions, which means creating an industry the size of the auto industry—along with consuming the associated resources—within the next decade. Improving DAC processes via scale is not enough; focusing on breakthroughs in sorbent performance is needed to reduce the number of systems and sheer volume of resources needed to rapidly bring DAC to the scales required to prevent further climate change. There are roles for government, corporations, and the carbon removal industry to play in enabling infrastructure, increasing demand, and creating clarity to accelerate deployment of DAC and, more broadly, carbon dioxide removal technologies.

Heparanase is the sole endoglucuronidase that degrades heparan sulfate in the cell surface and extracellular matrix (ECM). Several studies have reported the localization of heparanase in the cell nucleus, but the functional role of the nuclear enzyme is still obscure. Subjecting mouse embryonic fibroblasts (MEFs) derived from heparanase knockout (Hpse-KO) mice and applying transposase-accessible chromatin with sequencing (ATAC-seq), we revealed that heparanase is involved in the regulation of chromatin accessibility. Integrating with genome-wide analysis of chromatin states revealed an overall low activity in the enhancer and promoter regions of Hpse-KO MEFs compared with wild-type (WT) MEFs. Western blot analysis of MEFs and tissues derived from Hpse-KO vs. WT mice confirmed reduced expression of H3K27ac (acetylated lysine at N-terminal position 27 of the histone H3 protein). Our results offer a mechanistic explanation for the well-documented attenuation of inflammatory responses and tumor growth in Hpse-KO mice.