Search

LEGEND searches for lepton number violation in neutrinoless double beta (0νββ) decay using $^{76}$Ge-enriched high-purity germanium (HPGe) detectors immersed in liquid argon. The first stage, LEGEND-200, will operate 200 kg of detectors, a significant fraction of which are the new large Inverted Coaxial Point Contact (ICPC) detectors currently under production. An extensive characterization campaign to determine the basic operational parameters of the newly produced detectors is performed in vacuum cryostats at two underground sites in order to reduce the internal creation of cosmogenic radionuclides. Other dedicated scanning setups are used to obtain a detailed understanding of alpha and beta surface events on the p+ and n+ contacts which are projected to be the dominant backgrounds for the 0νββ decay search. This poster will present the production experience of the new ICPC detectors, the ongoing characterization campaigns, and the projected detector performances based on recent measurements.

Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself.We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non-dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years.Patients with CV44.2% and TTR40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV44.2% (lower intrapatient variability).These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non-dose-corrected TAC levels irrespective of reason or indication.

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions., Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revisions

The population of patients with kidney transplants in the United States is growing. The delivery of transplant care is complex, involves a multidisciplinary transplant team, and care coordination between transplant and community providers. The transplant nephrologist is central to the delivery of this care and assumes a multitude of clinical and nonclinical roles and responsibilities. With a growing population of patients requiring transplant care that spans a continuum from pretransplant referral to long-term posttransplant management, an understanding of the current state of the transplant nephrology workforce in the United States and the future that it faces is important in ensuring that current and future needs of both patients and physicians are met. In this article, we (1) review the scope of practice of the transplant nephrologist, (2) discuss the state of training in the field of transplant nephrology, (3) review the role of the referring primary nephrologist in the care of patients undergoing kidney transplant, and (4) discuss challenges and opportunities facing the transplant nephrology workforce.

As the medical community is increasingly offering transplantation to patients with increasing comorbidity burdens, the number of simultaneous heart-kidney (SHK) transplants is rising in the United States. How to determine eligibility for SHK transplant versus heart transplant alone is unknown. In this review, we situate this problem in the broader picture of organ shortage. We critically appraise available literature on outcomes in SHK versus heart transplant alone. We posit staged kidney-after-heart transplantation as a plausible alternative to SHK transplantation and review the pros and cons. Drawing lessons from the field of simultaneous liver-kidney transplant, we argue for an analogous policy for SHK transplant with standardized minimal eligibility criteria and a modified Safety Net provision. The new policy will serve as a starting point for comparing simultaneous versus staged approaches and refining the medical eligibility criteria for SHK.

The MAJORANA DEMONSTRATOR is an experiment constructed to search for neutrinoless double-beta decays in germanium-76 and to demonstrate the feasibility to deploy a ton-scale experiment in a phased and modular fashion. It consists of two modular arrays of natural and $^{76}\textrm{Ge}$-enriched germanium detectors totaling 44.1 kg (29.7 kg enriched detectors), located at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. Data taken with this setup since summer 2015 at different construction stages of the experiment show a clear reduction of the observed background index around the ROI for $0\nu\beta\beta$-decay search due to improvements in shielding. We discuss the statistical approaches to search for a $0\nu\beta\beta$-signal and derive the physics sensitivity for an expected exposure of $10\,\textrm{kg}{\cdot}\textrm{y}$ from enriched detectors using a profile likelihood based hypothesis test in combination with toy Monte Carlo data., Comment: 5 page, 2 figures, to appear in Proceedings of TAUP 2017 - XV International Conference on Topics in Astroparticle and Underground Physics, 24 - 28 July 2017, Sudbury, ON, Canada

We report on the preparation of and calibration measurements with a $^{83\mathrm{m}}$Kr source for the CENNS-10 liquid argon detector. $^{83\mathrm{m}}$Kr atoms generated in the decay of a $^{83}$Rb source were introduced into the detector via injection into the Ar circulation loop. Scintillation light arising from the 9.4 keV and 32.1 keV conversion electrons in the decay of $^{83\mathrm{m}}$Kr in the detector volume were then observed. This calibration source allows the characterization of the low-energy response of the CENNS-10 detector and is applicable to other low-energy-threshold detectors. The energy resolution of the detector was measured to be 9$\%$ at the total $^{83\mathrm{m}}$Kr decay energy of 41.5 keV. We performed an analysis to separately calibrate the detector using the two conversion electrons at 9.4 keV and 32.1 keV, Comment: v2: As accepted to JINST

The MAJORANA DEMONSTRATOR is an experiment constructed to search for neutrinoless double-beta decays in germanium-76 and to demonstrate the feasibility to deploy a large-scale experiment in a phased and modular fashion. It consists of two modular arrays of natural and $^{76}$Ge-enriched germanium detectors totalling 44.1 kg, located at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. Any neutrinoless double-beta decay search requires a thorough understanding of the background and the signal energy spectra. The various techniques employed to ensure the integrity of the measured spectra are discussed. Data collection is monitored with a thorough set of checks, and subsequent careful analysis is performed to qualify the data for higher level physics analysis. Instrumental background events are tagged for removal, and problematic channels are removed from consideration as necessary., Comment: 5 pages, 2 figures, Proceedings of TAUP 2017 - XV International Conference on Topics in Astroparticle and Underground Physics (Sudbury ON, Canada, July 24-28, 2017)

Neutrinoless double-beta decay searches seek to determine the nature of neutrinos, the existence of a lepton violating process, and the effective Majorana neutrino mass. The {\sc Majorana} Collaboration is assembling an array of high purity Ge detectors to search for neutrinoless double-beta decay in $^{76}$Ge. The {\sc Majorana Demonstrator} is composed of 44.8~kg (29.7 kg enriched in $^{76}$Ge) of Ge detectors in total, split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. The initial goals of the {\sc Demonstrator} are to establish the required background and scalability of a Ge-based, next-generation, tonne-scale experiment. Following a commissioning run that began in 2015, the first detector module started physics data production in early 2016. We will discuss initial results of the Module 1 commissioning and first physics run, as well as the status and potential physics reach of the full {\sc Majorana Demonstrator} experiment. The collaboration plans to complete the assembly of the second detector module by mid-2016 to begin full data production with the entire array., Neutrino 2016 proceeding

Intravenous immunoglobulin is a recognized treatment in recalcitrant autoimmune bullous diseases. Infusions are administered monthly over 1–5 days in the hospital setting and associated with mild to severe infusion-related systemic effects, in part due to the high doses necessary to induce and achieve remission. We present a case series of four patients with bullous diseases treated successfully with low-dose subcutaneous IgG who achieved remission with maintenance therapy. Patient-administered smaller, more frequent doses of IgG into subcutaneous tissue more closely mimics the body’s own antibody production and produces a more stable serum trough level. Subcutaneous IgG is a novel treatment approach in bullous diseases which can induce a state remission.

Background: Acne vulgaris (acne), a common inflammatory skin disorder, has its peak incidence between 14 and 19 years of age, with girls frequently developing acne earlier than boys. Over recent years, persistent acne is becoming more prevalent in adult women. ----- Objectives: This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which nonprescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. ----- Methods: The best available evidence on nonprescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. ----- Results: All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, as per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Nonprescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use nonprescription acne treatment products in these patients. ----- Conclusion: The panel agreed that guidelines including nonprescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Individuals with progressive advanced chronic kidney disease (CKD) have a number of treatment modalities to consider before reaching end-stage renal disease. As CKD reaches stage 4, and particularly as glomerular filtration rate approaches 20 mL/min, patients should be informed of kidney transplantation as a treatment option, provided education regarding the transplant process, and be referred to a transplant center unless there are clear contraindications or comorbidities that preclude consideration. There is an unfortunate and dramatic disparity between those who are eligible for transplantation and those who receive a transplant, due in part to referral biases, the comparative shortage of deceased donors, and a lack of acceptance or awareness of living kidney donation as an option. This chapter reviews the transplant landscape, discusses the procedural and pathophysiological considerations for kidney transplantation, and outlines the transplant evaluation process, including inclusion and exclusion criteria.

Vandetanib is an oral tyrosine kinase inhibitor with cutaneous adverse effects that include the development of acne. We present a patient who underwent vandetanib therapy for stage IV medullary thyroid cancer in conjunction with the use of doxycycline for acne that developed. After vandetanib use, blue-grey pigmentation developed in the acne on his face, chest, back, and arms, which darkened after the use of doxycycline. We review the literature to report that this blue-grey hyperpigmentation was likely vandetanib-induced but may have been the result of both drugs being used in combination.

Background Young adults with end-stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact. Design A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi-structured interviews. Participants Young people with ESKD aged 18-30 years (N = 27), attending single-centre follow-up in Oxford, UK were matched with 27 comparable young people aged 19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver were selected for interview. Measurements Self-report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding. Results Sixty percent of non-student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty-four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment. Conclusion ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical outcomes.

The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation.In this single-center, prospective, open-label, parallel-group, randomized trial, 23 adult patients with ADPKD who successfully underwent renal transplantation from 2008 to 2012 were subsequently randomized (on a 1:1 basis) to a maintenance immunosuppression regimen with either sirolimus (sirolimus, tacrolimus, prednisone) or mycophenolate (mycophenolate, tacrolimus, prednisone). Total kidney volumes were measured by means of high-resolution magnetic resonance imaging within 2 weeks after transplantation and at 1 year. The primary end point was change in total kidney volume at 1 year.Sixteen patients completed the 1-year study (8 patients in each group). There was a decrease in kidney volume in both the sirolimus group (percentage change from baseline, 20.5%; P .001) and mycophenolate group (percentage change from baseline, 17%; P = .048), but there was no significant difference in percentage change of total kidney volume between the groups (P = .665).In ADPKD patients at 1 year after kidney transplantation, there was a similar decrease in polycystic kidney volume in patients receiving an immunosuppression regimen containing sirolimus compared with patients receiving mycophenolate.

Reduced-intensity conditioning regimens using fludarabine (Flu) and cyclophosphamide (Cy) have been widely used in hematopoietic cell transplantation (HCT) recipients. The optimal exposure of these agents remains to be determined. We aimed to delineate the exposure-outcome associations of Flu and Cy separately and then both combined on HCT outcomes. This is a single-center, observational, pharmacokinetic (PK)-pharmacodynamic (PD) study of Flu and Cy in HCT recipients age ≥18 years who received Cy (50 mg/kg in a single dose), Flu (150 to 200 mg/m(2) given as 5 daily doses), and total body irradiation (TBI; 200 cGy). We measured trough concentrations of 9-β-D-arabinosyl-2-fluorade-nine (F-ara-A), an active metabolite of Flu, on days −5 and −4 (F-ara-A(Day-5) and F-ara-A(Day-4), respectively), and measured phosphoramide mustard (PM), the final active metabolite of Cy, and estimated the area under the curve (AUC). The 89 enrolled patients had a nonrelapse mortality (NRM) of 9% (95% confidence interval [CI], 3% to 15%) at day +100 and 15% (95% CI, 7% to 22%) at day +180, and an overall survival (OS) of 73% (95% CI, 63% to 81%) at day +180. In multivariate analysis, higher PM area under the curve (AUC) for 0 to 8 hours (PM AUC(0–8 hr)) was an independent predictor of worse NRM (P < .01 at both day +100 and day +180) and worse day +180 OS (P < .01), but no associations were identified for F-ara-A trough levels. We observed lower day +100 NRM in those with both high F-ara-A(Day-4) trough levels (≥40 ng/mL; >25th percentile) and low PM AUC(0–8 hr) (16-fold higher NRM. These results warrant further investigation to optimize reduced-intensity regimens based on better PK-PD understanding and possible adaptation to predictable factors influencing drug clearance.

In this paper, we focus on monitoring, a particular aspect of reflection related to teaching. We define monitoring as a feedback mechanism which entails attending to and evaluating a multitude of cues in the envi- ronment in order to evaluate progress towards a goal. We direct our attention to monitoring because it is a way in which a teacher is able to gain understanding of how effective his/her teaching actions are. Thus, knowing what cues to evaluate (and being able to do so) is a critical skill in reflection. Further, we focus exclusively in this paper on the concur- rent monitoring of cues related to students since we believe that attention to student cues while teaching provides teachers with a window into their students' learning experiences. We call this particular type of reflection, reflection-in-action. As well as depicting multiple examples of monitoring drawn from our research, we explore the contribution of this work to the literature in higher education and to faculty development activities, particularly, to the growing literature on teacher thinking.

The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultralow background, 40-kg modular high purity Ge (HPGe) detector array to search for neutrinoless double-beta decay (0νββ-decay) in 76Ge. The goal of the experiment is to demonstrate a background rate at or below 3 counts/(t-y) in the 4 keV region of interest (ROI) around the 2039 keV Q-value for 76Ge 0νββ-decay. In this paper, the status of the MAJORANA DEMONSTRATOR, including its design and measurements of properties of the HPGe crystals is presented.

With physical education (PE) being an avenue to be physically active and learn about health and wellbeing, it is important to understand enrollment trends and physical activity (PA) behaviors among adolescents. The purpose of this study is to examine adolescents’ health profiles and gain an understanding of adolescents’ perspective of PE. The current study used mixed methodology to examine adolescents’ health profiles and gain understanding of their perspectives of PE. Part 1 identified relationships over a two-year period between: PE rating, physical activity (PA), and health variables using data from the National Longitudinal Survey of Children and Youth (NLSCY). Part 2 examined adolescents’ perspectives of PE through four focus groups.Overall, PE was preferred over other subjects by 78% of participants; and preferring PE predicted higher frequencies of PA, lower BMI, and higher self-esteem. Enrollment in high school PE was influenced by the environment, gender, course conflicts, and teacher influence. In summary, the majority of adolescents prefer PE; it has an influence on health, and is an avenue for PA. Continued efforts need to be made to increase PE enrollment and participation to ensure the health of young people.

To review recent pancreas transplantation outcomes and indications and describe studies of the impact of pancreas transplant upon patient survival and secondary complications.A number of surgical advances have occurred that have improved the early success rate of transplant, and modern immunosuppressive strategies have improved the rate of longer term allograft survival. Pancreas transplant is associated with a mortality benefit when performed in patients with end-stage renal disease in combination with kidney transplant, but questions regarding the impact upon secondary diabetic complications together with the risk assumed by the surgical procedure and the attendant immunosuppression in the nonuremic patient may have tempered enthusiasm for broader expansion of transplantation. Thus, despite these advances, the number of pancreas transplants performed annually is falling consistently. Efforts to define optimal donor and recipient characteristics and understand the pathophysiological impact of pancreas transplant are active areas of research that may lead to greater expansion of pancreas transplant in the future.The review summarizes these advances, including the utilization patterns of pancreas transplant and current concepts of patient selection and graft monitoring, and places into perspective the current and future role of pancreas transplantation as a therapeutic option in diabetes.

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research.

The MAJORANA DEMONSTRATOR is searching for neutrinoless double-beta decay in $^{76}$Ge with two modular arrays of natural and $^{76}$Ge-enriched germanium detectors. It is located at the 4850 level of Sanford Underground Research Facility in Lead, South Dakota, USA, and its total mass of germanium detectors is 44.1 kg, of which 29.7 kg is enriched. The analysis of the first 26 kg-yr of data provides an unprecedented energy resolution of 0.13% in the region of interest at 2039 keV and a background level of 15.4 $\pm$ 2.0 counts/(FWHM t yr). It establishes the lower limit of the half-life of neutrinoless double beta decay as 2.7 10$^{25}$ yr in 76Ge at 90% CL. This analysis will be summarized here with an emphasis on the energy determination., MEDEX'19 proceedings. Since it was send to AIP, the last reference was published: S. I. Alvis et al. (Majorana Collaboration) Phys. Rev. C 100, 025501

Author(s): Cuesta, C; Alvis, SI; Arnquist, IJ; Avignone, FT; Barabash, AS; Barton, CJ; Basu, V; Bertrand, FE; Bos, B; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Clark, M; Cuesta, C; Detwiler, JA; Efremenko, Y; Ejiri, H; Elliott, SR; Gilliss, T; Giovanetti, GK; Green, MP; Gruszko, J; Guinn, IS; Guiseppe, VE; Haufe, CR; Hegedus, RJ; Hehn, L; Henning, R; Hervas Aguilar, D; Hoppe, EW; Howe, MA; Kidd, MF; Konovalov, SI; Kouzes, RT; Lopez, AM; Martin, RD; Massarczyk, R; Meijer, SJ; Mertens, S; Myslik, J; Othman, G; Pettus, W; Piliounis, A; Poon, AWP; Radford, DC; Rager, J; Reine, AL; Rielage, K; Ruof, NW; Shanks, B; Shirchenko, M; Tedeschi, D; Varner, RL; Vasilyev, S; White, BR; Wilkerson, JF; Wiseman, C; Xu, W; Yakushev, E; Yu, CH; Yumatov, V; Zhitnikov, I; Zhu, BX | Abstract: The Majorana Collaboration is operating an array of high-purity Ge detectors to search for the neutrinoless double-β decay of Ge76. The Majorana Demonstrator consists of 44.1 kg of Ge detectors (29.7 kg enriched to 88% in Ge76) split between two modules constructed from ultraclean materials. Both modules are contained in a low-background shield at the Sanford Underground Research Facility in Lead, South Dakota. We present updated results on the search for neutrinoless double-β decay in Ge76 with 26.0±0.5 kg yr of enriched exposure. With the Demonstrator's energy resolution of 2.53 keV FWHM at Qββ, which is the best among all neutrinoless double-β decay experiments, we observe one event in the region of interest with 0.65 events expected from the estimated background, resulting in a lower limit on the Ge76 neutrinoless double-β decay half-life of 2.7×1025 yr [90% confidence level (CL)] with a median sensitivity of 4.8×1025 yr (90% CL). Depending on the matrix elements used, a 90% CL upper limit on the effective Majorana neutrino mass in the range of 200-433 meV is obtained. The measured background in the configurations with full shielding and optimized grounding is 11.9±2.0 counts/(FWHM t yr).

Simultaneous calcineurin inhibitor avoidance (CNIA) and early corticosteroid withdrawal (ESW) have not been achieved primarily due to excessive acute rejection. This trial compared 2 belatacept-based CNIA/ESW regimens with a tacrolimus-based ESW regimen. Kidney transplant recipients were randomized to receive alemtuzumab/belatacept, rabbit anti-thymocyte globulin (rATG)/belatacept, or rATG/tacrolimus. The combinatorial primary endpoint consisted of patient death, renal allograft loss, or a Modification of Diet in Renal Disease-calculated eGFR of

A retrospective analysis on 587 patients with chronic lymphocytic leukemia (CLL) assessed risk factors for skin cancer and the influence of skin cancers on survival and incidence of solid tumors (STs). Patients underwent skin surveillance and were followed for a median of 6.65 years. The relative risk for skin cancer increased prior to CLL diagnosis rising 4-fold one-year post-diagnosis. Independent predictors for skin cancer were male gender (

The MAJORANA DEMONSTRATOR is searching for neutrinoless double-beta decay in 76Ge using arrays of point-contact germanium detectors operating at the Sanford Underground Research Facility. Background results in the neutrinoless double-beta decay region of interest from data taken during construction, commissioning, and the start of full operations have been recently published. A pulse shape analysis cut applied to achieve this result, named AvsE, is described in this paper. This cut is developed to remove events whose waveforms are typical of multi-site energy deposits while retaining (90 +/- 3.5)% of single-site events. This pulse shape discrimination is based on the relationship between the maximum current and energy, and tuned using 228Th calibration source data. The efficiency uncertainty accounts for variation across detectors, energy, and time, as well as for the position distribution difference between calibration and $0\nu\beta\beta$ events, established using simulations., Comment: 8 pages, 8 figures

Successful simultaneous pancreas-kidney transplantation (SPK) improves quality-of-life and prolongs kidney allograft and patient survival in type-1 diabetic (T1DM) patients. However, the use of SPK in type-2 diabetic (T2DM) patients remains limited. We examined a national transplant registry for 35 849 T2DM kidney disease patients who received transplant between 2000 and 2016 and survived the first 3 months with a functioning kidney, and categorized as: deceased-donor kidney transplant alone (DD-KA, 68%), living-donor kidney transplant alone (LD-KA, 30%), or SPK (2%). Among SPK recipients, 6% had pancreas allograft failure within 3 months (SPK,P-) and 94% had a functional pancreas (SPK,P+). Associations of transplant type with kidney allograft failure and death (multivariable-adjusted hazard ratio, 95%LCL aHR95%UCL ), over follow-up through December 2018, were quantified by multivariable inverse probability of treatment weighted survival analyses. SPK recipients had better kidney graft and patient survival than LD-KA or DD-KA recipients. Compared to SPK,P+, DD-KA, or LD-KA recipients had significantly higher risk of kidney allograft failure (DD-KA: aHR 1.53 2.203.17 ; LD-KA: aHR 1.29 1.872.71 ) and death (DD-KA: aHR 2.12 3.255.00 ; LD-KA: aHR 1.54 2.353.59 ). SPK,P- recipients had significantly higher risk of death (aHR 1.68 3.306.50 ). Similar to T1DM, T2DM patients with SPK have a survival benefit compared to those with kidney transplant alone, but this benefit depends upon successful early pancreas function.

Background and objectives Hypertension in older kidney donor candidates is viewed as safe. However, hypertension guidelines have evolved and long-term outcomes have not been explored. We sought to quantify the 15-year risk of ESKD and mortality in older donors (≥50 years old) with versus those without hypertension. Design, setting, participants, & measurements A United States cohort of 24,533 older donors from 1999 to 2016, including 2265 with predonation hypertension, were linked to Centers for Medicare and Medicaid Services data and the Social Security Death Master File to ascertain ESKD development and mortality. The exposure of interest was predonation hypertension. From 2004 to 2016, hypertension was defined as documented predonation use of antihypertensive therapy, regardless of systolic BP or diastolic BP; from 1999 to 2003, when there was no documentation of antihypertensive therapy, hypertension was defined as predonation systolic BP ≥140 or diastolic BP ≥90 mm Hg. Results Older donors were 82% white, 6% black, 7% Hispanic, and 3% Asian. The median follow-up was 7.1 years (interquartile range, 3.4–11.1; maximum, 18). There were 24 ESKD and 252 death events during the study period. The 15-year risk of ESKD was 0.8% (95% confidence interval [95% CI], 0.4 to 1.6) for donors with hypertension (mean systolic BP, 138 mm Hg) versus 0.2% (95% CI, 0.1 to 0.4) for donors without hypertension (mean systolic BP, 123 mm Hg; adjusted hazard ratio, 3.04; 95% CI, 1.28 to 7.22; P=0.01). When predonation antihypertensive therapy was available, the risk of ESKD was 6.21-fold higher (95% CI, 1.20 to 32.17; P=0.03) for donors using antihypertensive therapy (mean systolic BP, 132 mm Hg) versus those not using antihypertensive therapy (mean systolic BP, 124 mm Hg). There was no significant association between donor hypertension and 15-year mortality (hazard ratio, 1.18; 95% CI, 0.84 to 1.66; P=0.34). Conclusions Compared with older donors without hypertension, older donors with hypertension had higher risk of ESKD, but not mortality, for 15 years postdonation. However, the absolute risk of ESKD was small.

Background: Atopic dermatitis (AD) is a chronic, relapsing, and remitting inflammatory skin disease with complex pathophysiology, primarily driven by type 2 inflammation. Existing guidelines often do not reflect all current therapeutic options and guidance on the practical management of patients with AD is lacking. Objectives: To develop practical, up-to-date guidance on the assessment and management of adult patients with AD. Methods: An expert panel of 17 Canadian experts, including 16 dermatologists and 1 allergist, with extensive clinical experience managing moderate-to-severe AD reviewed the available literature from the past 5 years using a defined list of key search terms. This literature, along with clinical expertise and opinion, was used to draft concise, clinically relevant reviews of the current literature. Based on these reviews, experts developed and voted on recommendations and statements to reflect the practical management of adult patients with AD as a guide for health care providers in Canada and across the globe, using a prespecified agreement cutoff of 75%. Results: Eleven consensus statements were approved by the expert panel and reflected 4 key domains: pathophysiology, assessment, comorbidities, and treatment. Conclusions: These statements aim to provide a framework for the assessment and management of adult patients with AD and to guide health care providers in practically relevant aspects of patient management.

Both acute and chronic kidney disease are common after liver transplantation and result in significant morbidity and mortality. The introduction of the Model for End-stage Liver Disease score has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplantations performed. Kidney dysfunction in this population is typically multifactorial and related to preexisting conditions, pretransplantation renal injury, perioperative events, and posttransplantation nephrotoxic immunosuppressive therapies. The management of kidney disease after liver transplantation is challenging, as by the time the serum creatinine level is significantly elevated, few interventions affect the course of progression. Also, immunological factors such as antibody-mediated kidney rejection have become of greater interest given the rising liver-kidney transplant population. Therefore, this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestine Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine

The MAJORANA Collaboration is constructing the MAJORANA Demonstrator, an ultra-low background, 44-kg modular high-purity Ge (HPGe) detector array to search for neutrinoless double-beta decay in Ge-76. The phenomenon of surface micro-discharge induced by high-voltage has been studied in the context of the MAJORANA Demonstrator. This effect can damage the front-end electronics or mimic detector signals. To ensure the correct performance, every high-voltage cable and feedthrough must be capable of supplying HPGe detector operating voltages as high as 5 kV without exhibiting discharge. R&D measurements were carried out to understand the testing system and determine the optimum design configuration of the high-voltage path, including different improvements of the cable layout and feedthrough flange model selection. Every cable and feedthrough to be used at the MAJORANA Demonstrator was characterized and the micro-discharge effects during the MAJORANA Demonstrator commissioning phase were studied. A stable configuration has been achieved, and the cables and connectors can supply HPGe detector operating voltages without exhibiting discharge., 9 pages, 12 figures, 8 tables, submitted to NIM A

We have developed an unattended sensor for detecting anomalous radiation sources. The system combines several technologies to reduce size and weight, increase battery lifetime, and improve decision-making capabilities. Sixteen Cs2LiYCl6:Ce (CLYC) scintillators allow for gamma-ray spectroscopy and neutron detection in the same volume. Low-power electronics for readout, high voltage bias, and digital processing reduce the total operating power to 1.7 W. Computationally efficient analysis algorithms perform spectral anomaly detection and isotope identification. When an alarm occurs, the system transmits alarm information over a cellular modem. In this paper, we describe the overall design of the unattended sensor, present characterization results, and compare the performance to stock NaI:Tl and 3He detectors.

Two common polymorphisms in APOL1 (G1 and G2) are conserved in persons of African ancestry, and the presence of two polymorphisms (commonly referred to as risk variants) has been identified as a risk factor for chronic kidney disease and focal seg-mental glomerulosclerosis. In kidney transplantation, deceased donors with two APOL1 risk variants carry an increased risk of renal allograft failure in the recipient. An emerging question is whether these data should influence deceased donor assessment or be used to refine prediction of allograft survival. We present the first detailed report of two cases of recipient glomerular disease in the first year following transplant from a deceased donor later defined as carrying two APOL1 risk variants. A possible "second hit" predisposing to renal disease in these recipients is discussed, one with active cytomegalovirus infection concurrent with collapsing glomerulopathy and renal failure and the other with chronic, slowly healing wound infection and focal segmental glomeru-losclerosis but stable renal function. In retrospect, awareness of the donor APOL1 risk alleles would not have influenced donor selection and ultimately did not influence posttransplant management. These case reports inform further discussion of the value of APOL1 testing for deceased donors.

Past and current pressure on streams and rivers for consumptive use requires the development of tools and decision-making processes for water managers to minimize impacts on ecological function. This paper examines the utility of modeling benthic biomass in relation to benthic macroinvertebrate (BMI) community attributes for water resource management scenarios in the Cliff-Gila Valley of the Gila River, New Mexico, USA. The river benthos biomass model (RivBio) was used in conjunction with hydraulic modeling to predict growth and decline of benthic biomass. BMI community attributes were compared along gradients of hydrologic impact (successive existing diversions) in the Cliff Gila Valley and were compared to community attributes in similar regional streams. Benthic biomass was minimally affected by proposed diversions at flows above 4.25 cms (150 cfs), but was severely reduced downstream because of existing diversions during lower flow periods. Riffle habitat was disproportionately affected during extreme low and interrupted flow, which may have resulted in BMI communities shifted towards multi-habitat generalists that can persist in lentic conditions. Flow augmentation from proposed diversions and storage would greatly mitigate these existing biomass losses by providing consistent base flow and lotic conditions in riffle habitat. Both benthic biomass and BMI community endpoints were useful when comparing water management scenarios. Copyright © 2016 John Wiley & Sons, Ltd.

Immunosuppressive agents are commonly used in the nephrologist’s practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.

not available.

Author(s): Guinn, IS; Arnquist, IJ; Avignone, FT; Barabash, AS; Barton, CJ; Bertrand, FE; Bos, B; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Clark, ML; Cuesta, C; Detwiler, JA; Drobizhev, A; Edwins, DW; Efremenko, Y; Ejiri, H; Elliott, SR; Gilliss, T; Giovanetti, GK; Green, MP; Gruszko, J; Guiseppe, VE; Haufe, CR; Hegedus, RJ; Henning, R; Hervas Aguilar, D; Hoppe, EW; Hostiuc, A; Kidd, MF; Kim, I; Kouzes, RT; Lopez, AM; Lopez-Castano, JM; Martin, EL; Martin, RD; Massarczyk, R; Meijer, SJ; Mertens, S; Myslik, J; Oli, TK; Othman, G; Pettus, W; Poon, AWP; Radford, DC; Rager, J; Reine, AL; Rielage, K; Ruof, NW; Stortini, MJ; Tedeschi, D; Varner, RL; Wilkerson, JF; Wiseman, C; Xu, W; Yu, CH; Zhu, BX | Abstract: The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved.

Author(s): Gilliss, T; Abgrall, N; Alvis, SI; Arnquist, IJ; Avignone, FT; Barabash, AS; Barton, CJ; Bertrand, FE; Bode, T; Bradley, AW; Brudanin, V; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Cuesta, C; Detwiler, JA; Dunagan, C; Efremenko, Y; Ejiri, H; Elliott, SR; Giovanetti, GK; Green, MP; Gruszko, J; Guinn, IS; Guiseppe, VE; Haufe, CR; Hehn, L; Henning, R; Hoppe, EW; Howe, MA; Keeter, KJ; Kidd, MF; Konovalov, SI; Kouzes, RT; Lopez, AM; Martin, RD; Massarczyk, R; Meijer, SJ; Mertens, S; Myslik, J; O'Shaughnessy, C; Othman, G; Pettus, W; Poon, AWP; Radford, DC; Rager, J; Reine, AL; Rielage, K; Robertson, RGH; Ruof, NW; Shanks, B; Shirchenko, M; Suriano, AM; Tedeschi, D; Trimble, JE; Varner, RL; Vasilyev, S; Vetter, K; Vorren, K; White, BR; Wilkerson, JF; Wiseman, C; Xu, W; Yakushev, E; Yu, CH; Yumatov, V; Zhitnikov, I; Zhu, BX | Abstract: The MAJORANA DEMONSTRATOR is a 76Ge-based neutrinoless double-beta decay (0νββ) experiment. Staged at the 4850 ft level of the Sanford Underground Research Facility, the DEMONSTRATOR operates an array of high-purity p-Type point contact Ge detectors deployed within a graded passive shield and an active muon veto system. The present work concerns the two-neutrino double-beta decay mode (2νββ) of 76Ge. For Ge detectors, having superior energy resolution (0.1%), this mode poses negligible background to the 0νββ mode, even for a ton-scale experiment. However, the measurement of the 2νββ mode allows for careful systematics checks of active detector mass, enrichment fraction, and pulse shape discrimination cuts related to both the 0νββ and 2νββ decay modes. A precision measurement of the 2νββ shape also allows searches for spectral distortions, possibly indicative of new physics, including 0νββχ. Work is underway to construct a full experimental background model enabling a Bayesian fit to the measured energy spectrum and extraction of a precise 2νββ spectrum and half-life.

Author(s): Elliott, SR; Abgrall, N; Arnquist, IJ; Avignone, FT; Barabash, AS; Bertrand, FE; Bradley, AW; Brudanin, V; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Cuesta, C; Detwiler, JA; Dunagan, C; Efremenko, Y; Ejiri, H; Fullmer, A; Galindo-Uribarri, A; Gilliss, T; Giovanetti, GK; Green, MP; Gruszko, J; Guinn, IS; Guiseppe, VE; Henning, R; Hoppe, EW; Howe, MA; Jasinski, BR; Keeter, KJ; Kidd, MF; Konovalov, SI; Kouzes, RT; Leon, J; Lopez, AM; Macmullin, J; Martin, RD; Massarczyk, R; Meijer, SJ; Mertens, S; Orrell, JL; O'Shaughnessy, C; Poon, AWP; Radford, DC; Rager, J; Rielage, K; Robertson, RGH; Romero-Romero, E; Shanks, B; Shirchenko, M; Suriano, AM; Tedeschi, D; Trimble, JE; Varner, RL; Vasilyev, S; Vetter, K; Vorren, K; White, BR; Wilkerson, JF; Wiseman, C; Xu, W; Yakushev, E; Yu, CH; Yumatov, V; Zhitnikov, I | Abstract: Neutrinoless double-beta decay searches seek to determine the nature of neutrinos, the existence of a lepton violating process, and the effective Majorana neutrino mass. The Majorana Collaboration is assembling an array of high purity Ge detectors to search for neutrinoless double-beta decay in 76Ge. The Majorana Demonstrator is composed of 44.8 kg (29.7 kg enriched in 76Ge) of Ge detectors in total, split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. The initial goals of the Demonstrator are to establish the required background and scalability of a Ge-based, next-generation, tonne-scale experiment. Following a commissioning run that began in 2015, the first detector module started physics data production in early 2016. We will discuss initial results of the Module 1 commissioning and first physics run, as well as the status and potential physics reach of the full Majorana Demonstrator experiment. The collaboration plans to complete the assembly of the second detector module by mid-2016 to begin full data production with the entire array.

Author(s): Haufe, CR; Reine, AL; Abgrall, N; Alvis, SI; Arnquist, IJ; Avignone, FT; Barabash, AS; Barton, CJ; Bertrand, FE; Bode, T; Bradley, AW; Brudanin, V; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Cuesta, C; Detwiler, JA; Dunagan, C; Efremenko, Y; Ejiri, H; Elliott, SR; Gilliss, T; Giovanetti, GK; Green, MP; Gruszko, J; Guinn, IS; Guiseppe, VE; Hehn, L; Henning, R; Hoppe, EW; Howe, MA; Keeter, KJ; Kidd, MF; Konovalov, SI; Kouzes, RT; Lopez, AM; Martin, RD; Massarczyk, R; Meijer, SJ; Mertens, S; Myslik, J; O'Shaughnessy, C; Othman, G; Pettus, W; Poon, AWP; Radford, DC; Rager, J; Rielage, K; Robertson, RGH; Ruof, NW; Shanks, B; Shirchenko, M; Suriano, AM; Tedeschi, D; Trimble, JE; Varner, RL; Vasilyev, S; Vetter, K; Vorren, K; White, BR; Wilkerson, JF; Wiseman, C; Xu, W; Yakushev, E; Yu, CH; Yumatov, V; Zhitnikov, I; Zhu, BX | Abstract: The MAJORANA DEMONSTRATOR is an experiment constructed to search for neutrinoless double-beta decays in germanium-76 and to demonstrate the feasibility to deploy a ton-scale experiment in a phased and modular fashion. It consists of two modular arrays of natural and 76Ge-enriched germanium p-Type point contact detectors totaling 44.1 kg, located at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. The DEMONSTRATOR uses custom high voltage cables to bias the detectors, as well as custom signal cables and connectors to read out the charge deposited at each detectors point contact. These low-mass cables and connectors must meet stringent radiopurity requirements while being subjected to thermal and mechanical stress. A number of issues have been identified with the currently installed cables and connectors. An improved set of cables and connectors for the MAJORANA DEMONSTRATOR are being developed with the aim of increasing their overall reliability and connectivity. We will discuss some of the issues encountered with the current cables and connectors as well as our improved designs and their initial performance.

Young adults with end-stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact.A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi-structured interviews.Young people with ESKD aged 18-30 years (N = 27), attending single-centre follow-up in Oxford, UK were matched with 27 comparable young people aged 19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver were selected for interview.Self-report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding.Sixty percent of non-student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty-four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment.ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical outcomes.

Purpose of review To define the natural history of kidney allograft loss related to recurrent diabetes following transplant, and to understand the potential benefit of pancreas transplantation upon kidney allograft survival. Recent findings A postulated benefit of simultaneous pancreas kidney transplant is that, unlike kidney transplant alone, euglycemia from the added pancreas allograft may confer a nephroprotective benefit and prevent recurrent diabetic nephropathy in the renal allograft. Recent large database analyses and long-term histological assessments have been published that assist in quantifying the problem of recurrent diabetic nephropathy and answering the question of the potential benefits of euglycemia. Further data may be extrapolated from larger single-center series that follow the prognosis of early posttransplant diabetes mellitus as another barometer of risk from diabetic nephropathy and graft loss. Summary Recurrent diabetic nephropathy following kidney transplant is a relatively rare, late occurrence and its clinical significance is significantly diminished by the competing risks of death and chronic alloimmune injury. Although there are hints of a protective effect upon kidney graft survival with pancreas transplant, these improvements are small and may take decades to appreciate. Clinical decision-making regarding pancreas transplant solely based upon nephroprotective effects of the kidney allograft should be avoided.

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.

The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in [superscript 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., National Science Foundation (U.S.) (Grant MRI-0923142), National Science Foundation (U.S.) (Grant PHY-1003399), National Science Foundation (U.S.) (Grant PHY-1102292), National Science Foundation (U.S.) (Grant PHY1206314), National Science Foundation (U.S.) (Grant PHY-1614611), Los Alamos National Laboratory. Laboratory Directed Research and Development Program, Pacific Northwest National Laboratory (U.S.). Laboratory Directed Research and Development Program, Russian Foundation for Basic Research (Grant 15-02- 02919), Natural Sciences and Engineering Research Council of Canada (SAPIN-2017-00023), Canada Foundation for Innovation