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Chronic kidney disease (CKD) after solid organ transplant is a common clinical presentation, affecting 10% to 20% of liver, heart, and lung transplant recipients and accounting for approximately 5% of the kidney transplant waiting list. The causes of CKD are different for different types of transplants and are not all, or even predominantly, due to calcineurin inhibitor toxicity, with significant heterogeneity particularly in liver transplant recipients. Many solid organ transplant recipients with advanced CKD benefit from kidney transplantation but have a higher rate of death while waitlisted and higher mortality after transplant than the general kidney failure population. Recent organ allocation policies and proposals have attempted to address the appropriate identification and prioritization of candidates in need of a kidney transplant, either simultaneous with or after nonkidney transplant. Future research should focus on predictive factors for individuals identified as being at high risk for progression to kidney failure and death and on strategies to preserve kidney function and minimize the CKD burden in this unique patient population.

The Iroquoian and Algonquian-speaking Peoples of North America discovered numerous natural treatments to dermatological conditions long prior to European settlement. Anthropological evidence suggests that treatments for atopic dermatitis, dermatophyte infections, and syphilitic lesions were derived from Sassafras albidum, genus Salix trees, and S assafras officinale. Literature suggests these medicinal properties are attributed to the naturally abundant safrole, salicylic acid, and ascorbic acid in these flora. Numerous instances of these natural medicinal discoveries later being implemented into European literature reaffirms the impact of Indigenous medicine on contemporary dermatology.

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment’s high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay $Q$ value.

Background Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited. Objectives To measure the impact of adalimumab on moderate-to-severe HS patients’ health-related quality of life (HRQoL) and work productivity. Methods In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician’s practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6–10, medium; ≥11, high). Results From baseline to weeks 24 and 52, all PRO overall scores improved significantly ( P ≤ .0023). The number of patients reporting “good disease control” and “complete disease control” increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin “tenderness” and “itchiness” improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders. Conclusion At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients.

There are no standardized benchmarks to measure productivity and compensation of transplant nephrologists in the United States, and consequently, criteria set for general nephrologists are often used.A web-based survey was sent to 809 nephrologists who were members of the American Society of Transplantation to gather data on measures of productivity, compensation, and job satisfaction. Factors associated with higher total compensation and job satisfaction were examined.Of 365 respondents, 260 were actively practicing in the United States and provided data on compensation. Clinical productivity was assessed variably, and although 194 (76%) had their work relative value units (wRVUs) reported to them, only 107 (44%) had an established RVU target; 234 (90%) had fixed base compensation, and 172 (66%) received a bonus on the basis of clinical workload (68%), academic productivity (31%), service (32%), and/or teaching responsibility (31%). Only 127 respondents (49%) filled out time studies, and 92 (35%) received some compensation for nonbillable transplant activity. Mean total compensation (base salary and bonus) was $274,460±$91,509. The unadjusted mean total compensation was higher with older age and was higher for men; Hispanic and White respondents; adult care transplant nephrologists; residents of the western United States; US medical school graduates; nonuniversity hospital employees; and those with an administrative title, higher academic rank, and a higher number of years in practice. Two hundred and nine respondents (80%) thought their compensation was unfair, and 180 (70%) lacked a clear understanding of how they were compensated. One hundred forty-five respondents (55%) reported being satisfied or highly satisfied with their job. Job satisfaction was greater among those with higher amounts of compensation and US medical school graduates.We report significant heterogeneity in the assessment of productivity and compensation for transplant nephrologists and the association of compensation with job satisfaction.

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

The clinical importance of subclinical, early T cell–mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor‐derived cell‐free DNA (dd‐cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd‐cfDNA. Forty‐two patients had elevated dd‐cfDNA (≥0.5%) and 37 patients had low levels (, Among patients with borderline and 1A T cell–mediated rejection, a threshold of ≥ 0.5% of donor‐derived cell‐free DNA was associated with increased risk of renal function decline, donor‐specific antibody development, and future episodes of recurrent rejection.

We detail the design of a variable energy, x-ray fluorescence source using a low activity (1.8$\times10^6$~dpm) \nuc{99}{Tc} $\beta$ source that irradiates thin foils. By rotating the source among foils of Ti, Zn, Nb, Ag, and Au, the device produces x rays between 4 and 70 keV at a rate near 1 Hz. When the source is placed in a storage position, the external radiation is non-detectable. The design of the shielding and rotation mechanism permits use in vacuum and at liquid nitrogen temperature. The design is intended for the study of the low energy response to radiation impinging upon Ge detector surfaces. The source will be useful for understanding the detector response in large-scale Ge arrays such as \textsc{Majorana} and LEGEND., Comment: planned submission to JINST

This study aimed to 1) determine if post-concussion sleep quality of children and adolescents differed from healthy sleep estimates; 2) describe the trajectory of parameters of sleep quality; 3) determine factors that predict sleep quality outcomes; and 4) compare sleep parameter outcomes between asymptomatic and symptomatic participants at 4 weeks post-concussion. Nightly actigraphy estimates of sleep in 79 children and adolescents were measured throughout 4 weeks post-concussion. Total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of arousals (NOA), and average arousal length (AAL) were measured. Child and adolescent participants experienced significantly poorer SE and longer WASO duration throughout 4 weeks of recovery and adolescents experienced significantly longer TST. SE significantly improved with time post-injury (p = .047). Older age was associated with longer TST (p = .003) and female sex was associated with longer WASO (p = .025) and AAL duration (p = .044). Week 4 sleep parameter outcomes were not significantly different between asymptomatic and symptomatic participants. The sleep quality of youth is adversely affected by concussion, particularly in females. Sleep quality appears to improve with time but may require more than 4 weeks to return to normal.

The severe acute respiratory syndrome coronavirus 2 pandemic has necessitated enhanced protection against viral transmission among healthcare professionals, particularly relating to handwashing and personal protective equipment. Some of these requirements may persist for years to come. They bring associated concerns around skin hygiene and general care, with damage to the face and hands now a well-documented consequence among healthcare professionals. This review assesses optimal skin care during the severe acute respiratory syndrome coronavirus 2 pandemic and in the “new normal” that will follow, identifies current knowledge gaps, and provides practical advice for the clinical setting. Regular, systematic hand cleaning with soap and water or an alcohol-based hand rub (containing 60%–90% ethanol or isopropyl alcohol) remains essential, although the optimal quantity and duration is unclear. Gloves are a useful additional barrier; further studies are needed on preferred materials. Moisturization is typically helpful and has proven benefits in mitigating damage from frequent handwashing. It may be best practiced using an alcohol-based hand rub with added moisturizer and could be particularly important among individuals with pre-existing hand dermatoses, such as psoriasis and eczema. Face moisturization immediately prior to donning a mask, and the use of dressings under the mask to reduce friction, can be helpful dermatologically, but more work is required to prove that these actions do not affect seal integrity. Nonetheless, such measures could play a role in institutional plans for mitigating the dermatologic impact of transmission control measures as we exit the pandemic.

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D3 analogues. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift towards proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety.

Psoriasis is a chronic and debilitating inflammatory immune-mediated skin disorder. Several cytokines including interleukin (IL)-23 were demonstrated to play a central role in the pathogenesis of this disease. Treatment options for psoriasis range from topical to systemic modalities, depending on the extent, anatomical locations involved and functional impairment level. Targeting cytokines or their cognate receptors that are involved in disease pathogenesis such as IL-12/23 (i.e., targeting the IL-12p40 subunit shared by these cytokines), IL-17A, IL-17F, IL-17RA, and TNF-α using biologic agents emerged in recent years as a highly effective therapeutic option for patients with moderate-to-severe disease. This review provides an overview of the important role of IL-23 signaling in the pathogenesis of psoriasis. We describe in detail the available IL-23 inhibitors for chronic plaque psoriasis. The efficacy, pharmacokinetic properties, and the safety profile of one of the most recent IL-23 biologic agents (tildrakizumab) are evaluated and reviewed in depth.

The OPTN's simultaneous liver-kidney (SLK) allocation policy, implemented August 10, 2017, established medical eligibility criteria for adult SLK candidates and created Safety Net kidney allocation priority for liver-alone recipients with new/continued renal impairment. OPTN SLK and kidney after liver (KAL) data were analyzed (registrations as of December 31, 2019, transplants pre-policy [March 20, 2015-August 9, 2017] vs. post-policy [August 10, 2017-December 31, 2019]). Ninety-four percent of SLK registrations met eligibility criteria (99% CKD: 50% dialysis, 50% eGFR). SLK transplant volume decreased from a record 740 (2017) to 676 (2018, -9%), with a subsequent increase to 728 (2019, 1.6% below 2017 volume). For KAL listings within 1 year of liver transplant, waitlist mortality rates declined post-policy versus pre-policy (27 [95% CI = 20.6-34.7] vs. 16 [11.7-20.5]) while transplant rates increased fourfold (46 [32.2-60.0] vs. 197 [171.6-224.7]). There were 234 KAL transplants post-policy (94% Safety Net priority eligible), and no significant difference in 1-year patient/graft survival vs. kidney-alone (patient: 95.9% KAL, 97.0% kidney-alone [p = .39]; graft: 94.2% KAL, 94.6% kidney-alone [p = .81]). From pre- to post-policy, the proportion of all deceased donor kidney and liver transplants that were SLK decreased (kidney: 5.1% to 4.3%; liver: 9.7% to 8.7%). SLK policy implementation interrupted the longstanding rise in SLK transplants, while Safety Net priority directed kidneys to liver recipients in need with thus far minimal impact to posttransplant outcomes.

Highlights •CKD is associated with very high risk of CAD. CAD management is complicated in CKD patients, due to comorbid conditions and potential side effects during interventions. •There are few trials related to CAD with focus on CKD patients, particularly in those with advanced CKD. •Additional prospective studies focusing on diagnosis, prevention, and treatment of CAD are needed in CKD.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged

This document is a concise, current, and practical guide for dermatologists and other health care providers managing adult patients with moderate-to-severe atopic dermatitis (AD). The recommendations made here are based on a consensus of specialists with extensive experience managing patients with AD. Topics reviewed in this publication include AD pathophysiology, assessment, comorbidities, and treatment options.

Atopic dermatitis (AD) is often associated with other atopic diseases, including asthma, allergic rhinitis, atopy-associated eye disorders, and eosinophilic esophagitis. Depression and anxiety are also comorbidities to AD that significantly affect quality of life and should be screened for in patients with AD. Links to other comorbidities such as cardiovascular disease and malignancy are considered inconclusive, but patient counselling and screening may be appropriate in some patients. This article highlights practical recommendations for the recognition and management of atopic and nonatopic comorbidities commonly associated with AD.

The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.

The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5-8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor-based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.2%) completed the survey. A majority of respondents were older than 50 years (61%), males (80%), and holding that position for more than 10 years (47%). Only 51% of current medical directors had taken that position after completing a one-year transplant fellowship, and 58% took on the role with no prior administrative or leadership experience. The medical directors reported spending a median 50%-75% of time in clinical responsibilities, 25%-50% of time in administration, and 0%-25% time in research. The survey also captured various administrative roles of medical directors vis-a-vis other transplant leaders. The study, designed to be the starting point of an improvement initiative of the AST, provided important insight into the demographics, training pathways, roles and responsibilities, job satisfaction, education needs, and training gaps of current medical directors.

Background Long-term, real-word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease. Objectives To primarily measure real-world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients' response. Methods In SOLACE, adults with moderate-to-severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician's medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected. Results From 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected. Conclusions The effectiveness of adalimumab was maintained during this 1-year period, and an optimal gain was documented for patients with medium and high AN counts. These real-world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.

Author(s): Arnquist, IJ; Avignone, FT; Barabash, AS; Barton, CJ; Bertrand, FE; Blalock, E; Bos, B; Busch, M; Buuck, M; Caldwell, TS; Chan, YD; Christofferson, CD; Chu, PH; Clark, ML; Cuesta, C; Detwiler, JA; Drobizhev, A; Edwards, TR; Edwins, DW; Efremenko, Y; Ejiri, H; Elliott, SR; Gilliss, T; Giovanetti, GK; Green, MP; Gruszko, J; Guinn, IS; Guiseppe, VE; Haufe, CR; 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; Paudel, LS; Pettus, W; Poon, AWP; Radford, DC; Reine, AL; Rielage, K; Ruof, NW; Saykl, B; Stortini, MJ; Tedeschi, D; Varner, RL; Vasilyev, S; Wilkerson, JF; Wiseman, C; Xu, W; Yu, CH; Zhu, BX | Abstract: The majorana demonstrator is a neutrinoless double-β decay search consisting of a low-background modular array of high-purity germanium detectors, ∼2/3 of which are enriched to 88% in Ge76. The experiment is also searching for double-beta decay of Ge76 to excited states (e.s.) in Se76. Ge76 can decay into three daughter states of Se76, with clear event signatures consisting of a ββ-decay followed by the prompt emission of one or two γ rays. This results with high probability in multi-detector coincidences. The granularity of the demonstrator detector array enables powerful discrimination of this event signature from backgrounds. Using 41.9 kg yr of isotopic exposure, the demonstrator has set world leading limits for each e.s. decay of Ge76, with 90% CL lower half-life limits in the range of (0.75-4.0)×1024 yr. In particular, for the 2ν transition to the first 0+ e.s. of Se76, a lower half-life limit of 7.5×1023 yr at 90% CL was achieved.

We report on the technical design and expected performance of a 592 kg heavy-water-Cherenkov detector to measure the absolute neutrino flux from the pion-decay-at-rest neutrino source at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory (ORNL). The detector will be located roughly 20 m from the SNS target and will measure the neutrino flux with better than 5% statistical uncertainty in 2 years. This heavy-water detector will serve as the first module of a two-module detector system to ultimately measure the neutrino flux to 2-3% at both the First Target Station and the planned Second Target Station of the SNS. This detector will significantly reduce a dominant systematic uncertainty for neutrino cross-section measurements at the SNS, increasing the sensitivity of searches for new physics., Comment: As accepted to JINST

The management of a kidney transplant program has evolved significantly in the last decades to become a highly specialized, multidisciplinary standard of care for end-stage kidney disease. Transplant center job descriptions have similarly morphed with increasing responsibilities to address a more complex patient mix, increasing medical and surgical therapeutic options, and increasing regulatory burden in the face of an ever-increasing organ shortage. Within this evolution, the role of the Kidney Transplant Medical Director (KTMD) has expanded beyond the basic requirements described in the United Network for Organ Sharing bylaws. Without a clear job description, transplant nephrology trainees may be inadequately trained and practicing transplant nephrologists may face opaque expectations for the roles and responsibilities of Medical Director. To address this gap and clarify the key areas in which the KTMD interfaces with the kidney transplant program, American Society of Transplantation (AST) formed a Task Force of 14 AST KTMDs to review and define the role of the KTMD in key aspects of administrative, regulatory, budgetary, and educational oversight of a kidney transplant program.