Subsequent Rejection Research Articles

‘I Did Not Wash My Hand for Days’

This article focuses on the reception of revolutionary oratory in what was once known as The People’s Revolutionary Republic of Guinea. Sékou Touré, Guinea’s first president, captivated the nation with fiery, unscripted speeches lasting four, five, or six hours. Guinean audiences were enthralled by his sublime revolutionary rhetoric. In a 2008 coup, Captain Moussa Dadis Camara declared himself president, attempting to recreate the fervour of Guinea’s revolutionary days. Guinean citizens initially provided a willing revolutionary audience, though Camara’s oratory fell far short of Touré’s example. The article explores how the effects of shock and boredom that Ngai describes as ‘stuplimity’ (2005) emerged in reaction to Camara’s performances. Stuplimity was a halfway point between Guineans’ initial ‘revolutionary’ suspension of disbelief regarding the junta’s intentions and their subsequent rejection and anger, which led to the junta’s collapse less than a year after it took power.

Increasing the efficacy and safety of a human complement inhibitor for treating post-transplant cardiac ischemia reperfusion injury by targeting to a graft-specific neoepitope

Post-transplant ischemia reperfusion injury (IRI) is a recognized risk factor for subsequent organ dysfunction, alloresponsiveness, and rejection. The complement system is known to play a role in IRI and represents a therapeutic target. Complement is activated in transplanted grafts when circulating IgM antibodies bind to exposed ischemia-induced neoepitopes upon reperfusion, and we investigated the targeting of a human complement inhibitor, CR1, to a post-transplant ischemia-induced neoepitope. A fragment of human CR1 was linked to a single chain antibody construct (C2 scFv) recognizing an injury-specific neoepitope to yield C2-CR1. This construct, along with a soluble untargeted counterpart, was characterized in a cardiac allograft transplantation model of IRI in terms of efficacy and safety. CR1 was similarly effective against mouse and human complement. C2-CR1 provided effective protection against cardiac IRI at a lower dose than untargeted CR1. The increased efficacy of C2-CR1 relative to CR1 correlated with decreased C3 deposition, and C2-CR1, but not CR1, targeted to cardiac allografts. At a dose necessary to reduce IRI, C2-CR1 had minimal impact on serum complement activity, in contrast to CR1 which resulted in a high level of systemic inhibition. The circulatory half-life of CR1 was markedly longer than that of C2-CR1, and whereas a minimum therapeutic dose of CR1 severely impaired host susceptibility to infection, C2-CR1 had no impact. We show the translational potential of a human complement inhibitor targeted to a universal ischemia-induced graft-specific epitope, and demonstrate advantages compared to an untargeted counterpart in terms of efficacy and safety.

Non-Adherence to Appointments is a Strong Predictor of Medication Non-Adherence and Outcomes in Kidney Transplant Recipients

BackgroundNon-adherence is an important aspect of transplantation that affect outcomes. This study aims to investigate the impact of non-adherence to laboratory and clinic appointments on medication non-adherence and outcomes in kidney transplant (KT) recipients. MethodsWe analyzed KT recipients between 2005-14 with a detailed review of the medical records for non-adherence to laboratory and clinic appointments, as well as medication regimens. Baseline characteristics and clinical outcomes were compared between adherent and non-adherent groups. ResultsA total of 1413 KT recipients were included: 754 who were adherent and 659 who were non-adherent. Non-adherent recipients tend to be younger, African American, and have private insurance. Adherent patients tend to have a history of DM, heart disease, and receive an ECD kidney. Non-adherence to appointments was a strong predictor of medication non-adherence (OR 3.1), acute rejection (OR 1.4), and subsequent rejection episodes (OR 3.3 and 8.1 respectively for ≥ 1 and ≥ 2 rejection episodes). Subset analysis of patients who had early non-adherence within 1-year post-transplant showed predominance of younger, African American patients. The same patients had higher prevalence of medication non-compliance, overall and ≥ 1-year post-transplant, and mean number of readmissions. Kaplan-Meier analysis showed a trend towards lower graft survival in this group. ConclusionsEarly non-adherence to laboratory and clinic appointments is a strong predictor of late medication non-adherence, acute rejection, and graft loss. Targeting patients that demonstrate early non-adherence to appointments with focused interventions may help improve kidney transplant outcomes in this high risk group.

The clinical significance of receiving a kidney allograft from deceased donor with chronic histologic changes.

Allograft survival of deceased donor kidneys with suboptimal histology (DRTx/suboptimal histology: >10% glomerulosclerosis, >10% tubulointerstitial scarring, or >mild vascular sclerosis) is inferior to both DRTx with optimal histology (DRTx/optimal histology) and living donor kidneys irrespective of histologic changes (LRTx). In this report, we explored the reasons behind this guarded outcome with a special focus on the role of alloimmunity. We initially assessed gene expression in 39 time-zero allograft biopsies using the Nanostring 770 genes PanCancer Immune Profiling Panel. Subsequently, we studied 696 consecutive adult kidney allograft recipients that were grouped according to allograft type and histology at time-zero biopsy [DRTx/suboptimal histology (n = 194), DRTx/optimal histology (n = 166), and LRTx (n = 336)]. Part-1: Several immune pathways were upregulated in time-zero biopsies from DRTx/suboptimal histology (n = 11) compared to LRTx (n = 17) but not to DRTx/optimal histology (n = 11). Part-2: Amongst the three groups of recipients, DRTx/suboptimal histology had the highest incidence of acute rejection episodes, most of which occurred during the first year after transplantation (early rejection). This increase was mainly attributed to T cell mediated rejection, while the incidence of antibody-mediated rejection was similar amongst the three groups. Importantly, early acute T cell mediated rejection was a strong independent predictor for allograft failure in DRTx/suboptimal histology (adjusted HR: 2.13, P = 0.005) but not in DRTx/optimal histology nor in LRTx. Our data highlight an increased baseline immunogenicity in DRTx/suboptimal histology compared to LRTx but not to DRTx/optimal histology. However, our results suggest that donor chronic histologic changes in DRTx may help transfer such increased baseline immunogenicity into clinically relevant acute rejection episodes that have detrimental effects on allograft survival. These findings may provide a rationale for enhanced immunosuppression in recipients of DRTx with baseline chronic histologic changes to minimize subsequent acute rejection and to prolong allograft survival.

Lyell, the Geikies and Croll's observations on terrestrial glacial sediments and landforms

ABSTRACTWithin the context of the work and achievements of James Croll, this paper reviews the records of direct observations of glacial landforms and sediments made by Charles Lyell, Archibald and James Geikie and James Croll himself, in order to evaluate their contributions to the sciences of glacial geology and Quaternary environmental change. The paper outlines the social and physical environment of Croll's youth and contrasts this with the status and experiences of Lyell and the Geikies. It also outlines the character and role of the ‘Glasgow School’ of geologists, who stimulated Croll's interest into the causes of climate change and directed his focus to the glacial and ‘interglacial’ deposits of central Scotland. Contributions are outlined in chronological order, drawing attention to: (i) Lyell's high-quality observations and interpretations of glacial features in Glen Clova and Strathmore and his subsequent rejection of the glacial theory in favour of processes attributed to floating icebergs; (ii) the significant impact of Archibald Geikie's 1863 paper on the ‘glacial drift of Scotland’, which firmly established the land-ice theory; (iii) the fact that, despite James Croll's inherent dislike of geology and fieldwork, he provided high-quality descriptions and interpretations of the landforms and sediments of central Scotland in order to test his theory of climate change; and (iv) the great communication skills of James Geikie, enhanced by contacts and evidence from around the world. It is concluded that whilst direct observations of glacial landforms and sediments were critical to the long-term development of the study of glaciation, the acceptance of this theory was dependent also upon the skills, personality and status of the Geikies and Croll, who developed and promoted the concepts. Sadly, the subsequent rejection of the land-ice concept by Lyell resulted in the same factors challenging the acceptance of the glacial theory.

Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management.

Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection.

Research Highlights

Research Highlights

The Impact of Grade 1R Endomyocardial Biopsies on Donor-Derived Cell-Free DNA, Higher-Grade Rejection and Development of Donor Specific Antibodies

<h3>Purpose</h3> Recurrent episodes of mild rejection early post-transplant may lead to subsequent higher severity rejections and adverse outcomes, but there is a paucity of data on the prognosis of these patients. Elevations in donor-derived cell-free DNA (dd-cfDNA) and the development of donor specific antibodies (DSA) in kidney, heart, and lung transplantation have been described. We evaluated the association of AlloSure (dd-cfDNA) during episodes of acute cellular rejection (ACR) ISHLT Grade 1R with subsequent development of higher-grade rejections and DSA in heart transplantation. <h3>Methods</h3> This is a retrospective analysis of 484 patients who developed ACR Grade 1R (< 365 days post-transplant) paired with dd-cfDNA in the <i>Surveillance HeartCare® Outcomes Registry</i> (SHORE). dd-cfDNA levels were divided into 4 quartiles (median dd-cfDNA; Q1 = 0.10%, Q2 = 0.12%, Q3 = 0.15%, Q4 = 0.32%). The number of recurrent rejections (ISHLT Grade 2R/3R) and DSA were compared across quartiles using the Cochran-Armitage test (p<0.05). <h3>Results</h3> There were 933 episodes of Grade 1R biopsies. The median dd-cfDNA in 72 for-cause biopsies was 0.16% and in 860 surveillance biopsies was 0.12%, p=0.8979. Grade 1R rejection was not associated with later development of higher grades of ACR or dd-cfDNA quartiles (Table). Sixty-seven patients developed DSA subsequent to a 1R rejection and a higher incidence of DSA was associated with increased dd-cfDNA (median dd-cfDNA in Q1=8.7%, Q2=10.9%, Q3=18.9%, Q4=18.3%) (p = 0.006). <h3>Conclusion</h3> Grade 1R biopsies did not progress to higher grade rejections. There was no significant elevation in dd-cfDNA with Grade 1R biopsies. With increasing dd-cfDNA there was a significant trend toward DSA development following Grade 1R biopsies. Further analysis with longer follow-up to assess recurrent rejection and larger sample size of DSA is warranted.

Long-Term Effects of Monotherapy with Low Dose Tacrolimus

<h3>Purpose</h3> Monotherapy with tacrolimus alone (TAC-A) was found to be safe and effective in the TICTAC Trial. However, in that trial, tacrolimus levels were maintained at 10-12 ng/mL over the first year which resulted in a higher serum creatinine level compared to those left in combination. We have been using TAC-A at lower doses in patients who have developed leukopenia or thrombocytopenia due to immunosuppression or a natural state. The presence of cytomegalovirus infections and other viruses excluded those patients from being administered monotherapy. It has not been established whether low dose TAC-A is safe and effective. <h3>Methods</h3> Between 2010 and 2017 we assessed 151 heart transplant patients who are maintained on monotherapy with TAC-A. Patients were maintained on a low level of TAC-A between 4-7 ng/ml. These patients were assessed for subsequent 1-year rejection, subsequent 3-year survival, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), cardiac allograft vasculopathy (CAV, epicardial disease with angiographic stenosis>30%), and cardiac dysfunction (LVEF ≤ 40%). Furthermore, periodic testing was done with the T-cell immune function test to assess whether these patients were adequately immunosuppressed. <h3>Results</h3> Patients who were maintained on TAC-A had comparable outcomes compared to patients left in combination immunosuppression (see table). The T-cell immune function test showed that these patients had adequate immunosuppression (average was 276 ng/mL with a range of 56-794 ng/mL and standard deviation of 137.1 ng/mL) with the therapeutic range being 200-550ng/ml. Patients had an average of 11 Tacrolimus lab tests (range: 4-46). <h3>Conclusion</h3> Low dose TAC-A appears safe and effective in select patients after heart transplantation guided by T cell immune function testing. Further studies with larger number of patients will be needed to confirm these findings.

Six-Month Outcomes of Heart Transplant Recipients Infected by COVID-19

PurposeCOVID-19 infection might be associated with higher mortality risk for transplanted patients, as a result of their multiple co-morbidities and their immunosuppressed status. We sought to describe the six-month outcomes of heart transplant (HT) recipients infected by COVID-19.MethodsWe retrospectively analyzed clinical and echocardiographic data from all HT recipients infected with COVID-19 between March and April 2020. All patients were followed for a minimum of 6 months or until death.ResultsTwenty-eight HT patients were studied, median age was 64 (range 59-69) and 22 were male. Co-morbidities included obesity (25%), diabetes (61%), HTN (71%), CKD (68 %) and chronic lung disease (36%). Eight patients died (29%) (non-survivors) and 20 survived (survivors) COVID-19 infection. All patients who survived the initial hospitalization period remained alive at 6 months (figure 1). There was no difference in the prevalence of co-morbidities between survivors and non-survivors. Survivors had lower peak ferritin (2185 ± 793 vs 18023 ± 16724, p= 0.04) and procalcitonin (0.8 ± 0.3 vs 104 ± 31, p<0.005). Baseline allograft function was similar between survivors and non-survivors and it remained unchanged at 6 months for the survivors’ group (LVEF baseline: 58 ± 1% vs LVEF 6 m 61 ± 3%). Renal function returned to baseline in 85% of survivors at 6 months after hospitalization. Mycophenolate mofetil was held during the acute infection and was resumed after discharge. At 6 months follow-up, all patients returned to their baseline immunosuppression regimen, have no further symptoms of COVID-19 and there have been no subsequent rejection events.ConclusionCOVID-19 infection is associated with a high fatality rate (29%) among HT recipients, however, HT recipients that survive the acute COVID-19 infection have preserved allograft function and end-organ function has returned to baseline at 6 months follow-up.

Характеристики обнаружения когерентной системы селекции движущихся целей при рассогласовании параметров квадратурных каналов.

ntroduction. Operation of adaptive system of moving targets selection is considered, which is represented by single intermittent subtractor with coherent accumulator, which is tuned in frequency. System of moving targets selection is made in the form of two quadrature channels, in which high-frequency passive interference and signal from moving object are converted to video frequency with subsequent rejection, accumulation and comparison with threshold level. Setting the task. Investigation of the effect of the inevitable in practice amplitude and phase misalignments of quadrature channel parameters on the detection characteristics of the adaptive selection system of moving targets. Method. Method of complex variable is used, in which passive interference and signal from moving object at input and output of adaptive selection system of moving targets are presented in the form of pair of real components shifted in phase by ninety degrees. Results. Models of passive interference and signal from moving object are presented taking into account possible in practice amplitude and phase mismatches of quadrature channels parameters. The structure of the processing device is shown, which includes a series-connected generator of quadrature components of passive interference and a signal from a moving object, an adaptive cutting filter in the form of a single intermittent subtraction circuit with a frequency-tuned rejection zone, an adaptive coherent accumulator and a threshold device. Expressions are obtained for complex correlation functions of passive interference and signal from moving object at output of coherent accumulator taking into account inevitable amplitude and phase mismatches of quadrature channels parameters. Dependencies of probability of correct detection of signal from moving object against the background of passive interference from value of deviation of transmission coefficients of quadrature channels and phase mismatch of reference voltages for different values of average frequency of spectral density of passive interference are calculated and constructed. Conclusion. Significant dependence of probability of correct detection of signal from moving object on average frequency of spectral density of passive interference, as well as amplitude and phase mismatches of quadrature channels parameters is shown.

Transitional B cell cytokines predict renal allograft outcomes.

Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) produced by transitional-1 B cells (T1B) 3 months after transplantation as a predictive biomarker for clinical and subclinical renal allograft rejection and subsequent clinical course. In both Training (n = 162) and Internal Validation (n = 82) Sets, the T1B IL-10/TNFα ratio 3 months after transplantation predicted both clinical and subclinical rejection anytime in the first year. The biomarker also predicted subsequent late rejection with a lead time averaging 8 months. Among biomarker high-risk patients, 60% had early rejection, of which 48% recurred later in the first posttransplant year. Among high-risk patients without early rejection, 74% developed rejection later in the first year. In contrast, only 5% of low-risk patients had early and 5% late rejection. The biomarker also predicted rejection in an External Validation Set (n = 95) and in key patient subgroups, confirming generalizability. Biomarker high-risk patients exhibited progressively worse renal function and decreased 5-year graft survival compared to low-risk patients. Treatment of B cells with anti-TNFα in vitro augmented the IL-10/TNFα ratio, restored regulatory activity, and inhibited plasmablast differentiation. To conclude, the T1B IL-10/TNFα ratio was validated as a strong predictive biomarker of renal allograft outcomes and provides a rationale for preemptive therapeutic intervention with TNF blockade.

Dr James Ost’s contributions to the work of the British false memory society

ABSTRACT The British False Memory Society (BFMS) is a registered charity founded in 1993 in response to an epidemic of false claims of past childhood sexual abuse by adults in therapy. The accusers believe they have recovered unconscious memories of a hidden past, but scientific and other evidence raise the possibility of false memories or retrospective reappraisal. The BFMS aims to raise awareness about false memory and to reduce the impact of the resulting false accusations. Dr James Ost was an active member of the BFMS’s Scientific and Professional Advisory Board. Three lines of his research were particularly relevant to the work of the BFMS. The first of these was his investigations of retractors. His insights provided a deeper understanding of processes involved in the formation and subsequent rejection of false memories and beliefs relating to such allegations. He also carried out experimental studies providing empirical proof that false memories can be implanted under well controlled conditions. Finally, he carried out, and produced reviews of, surveys of misconceptions about the nature of memory, thus highlighting issues that have major implications for the working of the legal system. Dr Ost also served as an expert defence witness on a number of occasions.

BK Virus-Associated Nephropathy after Renal Transplantation.

Recent advances in immunosuppressive therapy have reduced the incidence of acute rejection and improved renal transplantation outcomes. Meanwhile, nephropathy caused by BK virus has become an important cause of acute or chronic graft dysfunction. The usual progression of infection begins with BK viruria and progresses to BK viremia, leading to BK virus associated nephropathy. To detect early signs of BK virus proliferation before the development of nephropathy, several screening tests are used including urinary cytology and urinary and plasma PCR. A definitive diagnosis of BK virus associated nephropathy can be achieved only histologically, typically by detecting tubulointerstitial inflammation associated with basophilic intranuclear inclusions in tubular and/or Bowman’s epithelial cells, in addition to immunostaining with anti-Simian virus 40 large T-antigen. Several pathological classifications have been proposed to categorize the severity of the disease to allow treatment strategies to be determined and treatment success to be predicted. Since no specific drugs that directly suppress the proliferation of BKV are available, the main therapeutic approach is the reduction of immunosuppressive drugs. The diagnosis of subsequent acute rejection, the definition of remission, the protocol of resuming immunosuppression, and long-term follow-up remain controversial.

Partially mismatched pediatric transplants with allogeneic CD34^+ blood cells from a related donor

This was a phase I, multi-center study of 13 pediatric patients (median age, 11 years) to evaluate toxicity, hematopoietic recovery, and graft-versus-host disease (GVHD) after allogeneic transplantation of enriched blood CD34(+) cells obtained from genotypically haploidentical but partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 microgram/kg/d for 5 days) and collected by 2 to 5 aphereses. To both enhance engraftment and reduce GVHD, CD34(+) cells were enriched using immunomagnetic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp, Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3(+) cells were infused. Using Center-specific posttransplant supportive care and immunosuppressive GVHD prophylaxis, two patients experienced early death; one from veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen in 4 patients, 2 of whom had autologous recovery. Eight patients were evaluated in the early phase of marrow recovery. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 (range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L was 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with functioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de novo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytomegalovirus infection was a major infectious complication but was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autologous origin. In conclusion, our results show that enriched blood CD34(+) cells from a mismatched haploidentical donor are a feasible alternative source of stem cells, but do not appear to ensure engraftment. Because none of the patients who were administered DLI survived, the therapeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies.

Populism and the evangelical church in Latin America: how anti-LGBTI forces tried to stop the Colombian peace agreement

The present paper explores the relationship between right-wing populism and the neo-Pentecostal Evangelical churches in Latin America, focusing on the anti-LGBT discourse emanating from this relationship. It argues that right-wing populists have been antagonizing the “people” against an imaginary LGBTI foe and using religious jargon and support to mobilize the masses against gender identity and sexual orientation achievements in the region. This argument is illustrated by a case study on one of the most emblematic moments of anti-LGBTI rhetoric in the last decade: the 2016 peace agreement referendum in Colombia. After more than fifty years of war between the FARC-EP and the government, a religious-populist movement claimed the Colombian peace agreement was tainted by “gender ideology”, which would threaten Colombian traditions and institutions. The 2016 referendum became a platform for advancing and repudiating LGBTI rights, and the subsequent rejection of the Colombian peace agreement is a case in point of the sharp opposition and "us vs them" narrative of right-populists and the neo-Pentecostal church against the LGBTI agenda.

EEG Integrated Platform Lossless (EEG-IP-L) pre-processing pipeline for objective signal quality assessment incorporating data annotation and blind source separation

BackgroundThe methods available for pre-processing EEG data are rapidly evolving as researchers gain access to vast computational resources; however, the field currently lacks a set of standardized approaches for data characterization, efficient interactive quality control review procedures, and large-scale automated processing that is compatible with High Performance Computing (HPC) resources. New MethodIn this paper we describe an infrastructure for the development of standardized procedures for semi and fully automated pre-processing of EEG data. Our pipeline incorporates several methods to isolate cortical signal from noise, maintain maximal information from raw recordings and provide comprehensive quality control and data visualization. In addition, batch processing procedures are integrated to scale up analyses for processing hundreds or thousands of data sets using HPC clusters. ResultsWe demonstrate here that by using the EEG Integrated Platform Lossless (EEG-IP-L) pipeline’s signal quality annotations, significant increase in data retention is achieved when applying subsequent post-processing ERP segment rejection procedures. Further, we demonstrate that the increase in data retention does not attenuate the ERP signal. ConclusionsThe EEG-IP-L state provides the infrastructure for an integrated platform that includes long-term data storage, minimal data manipulation and maximal signal retention, and flexibility in post processing strategies.

Primitivism in theZhuangzi: An introduction

AbstractBooks 8–10 and sections of books 11–16 of theZhuangzianthology represent an important and underappreciated contribution to Warring States ethical and political philosophy, known as “primitivism.” This article offers a general introduction to Zhuangist primitivism. It focuses on primitivism's exploration and development of a normative conception of human nature, particularlyxing性, as well as primitivism's subsequent rejection of the elaborate moral, social, political, and cultural artifices championed by their philosophical opponents, chiefly the Ruists and the Mohists. After a brief introduction to Zhuangist primitivism and the limited scholarship on it, I divide this discussion into three parts pertaining to the primitivists' three distinct approaches to and uses of human nature, which in turn serve as the basis for primitivist ethics and political thought.

Does the pressure to fill journal quotas bias evaluation?: Evidence from publication delays and rejection rates.

Although the peer review system of academic journals is seen as fundamental to scientific achievement, a major threat to the validity of the system is a potential evaluation bias resulting from constraints at the journal level. In this study, we examine how the time pressure to maintain a fixed periodical quota for journal publication can influence a journal editor's decision to accept or reject a paper at any given point in time. We find that an increase in publication backlog, proxied as the average delay between paper acceptance and print publication, is correlated with an increase in the subsequent rejection rates of new submissions. Our findings suggest that time pressures inherent in the peer review system may be a source of potential evaluator bias, calling for a need to reconsider the current quota system.

Transient behavior of two-stage load rejection for multiple units system in pumped storage plants

Pumped storage plants (PSPs) are being rapidly deployed and developed since they are cost-effective and mature energy storage solutions to the penetration of renewable energy sources (RES). Hydraulic transient analysis on PSPs, especially under extreme operating conditions such as two-stage load rejection (LR), is the key to safe hydraulic system design. Two-stage LR, involving a step-wise reduction in load, may induce extremely low draft tube pressure (DTP), directly threatening the safety of a multiple units PSP. Using numerical simulation, this study systematically investigates the behavior of the hydraulic parameters, and reveals the mechanism leading to the extremely low DTP during a two-stage LR process. The results indicate that the asynchronously varying discharge, coming from the inconsistent instants of time rejecting load and subsequent pressure difference, is the origin of severe reverse water hammer. Furthermore, the rate of discharge change of the subsequent load rejection turbine (SLRT) is confirmed to be the critical factor. The unexpected low DTP occurs exactly when its rate of discharge change reaches its minimum value. Additionally, the deeper the moving trajectory of the SLRT enters the reverse pump zone, the more severe the low DTP will be. Finally, two engineering measures that can economically and effectively improve the minimum DTP are proposed based on the hydraulic behavior of two-stage LR.