Streaming Property Testing of Visibly Pushdown Languages

In the context of language recognition, we demonstrate the superiority of streaming property testers against streaming algorithms and property testers, when they are not combined. Initiated by Feigenbaum et al., a streaming property tester is a streaming algorithm recognizing a language under the property testing approximation: it must distinguish inputs of the language from those that are $\varepsilon$-far from it, while using the smallest possible memory (rather than limiting its number of input queries). Our main result is a streaming $\varepsilon$-property tester for visibly pushdown languages (VPL) with one-sided error using memory space $\mathrm{poly}((\log n) / \varepsilon)$. This constructions relies on a (non-streaming) property tester for weighted regular languages based on a previous tester by Alon et al. We provide a simple application of this tester for streaming testing special cases of instances of VPL that are already hard for both streaming algorithms and property testers. Our main algorithm is a combination of an original simulation of visibly pushdown automata using a stack with small height but possible items of linear size. In a second step, those items are replaced by small sketches. Those sketches relies on a notion of suffix-sampling we introduce. This sampling is the key idea connecting our streaming tester algorithm to property testers.Comment: 23 pages. Major modifications in the presentatio

Streaming Property Testing of Visibly Pushdown Languages

In the context of formal language recognition, we demonstrate the superiority of streaming property testers against streaming algorithms and property testers, when they are not combined. Initiated by Feigenbaum et al., a streaming property tester is a streaming algorithm recognizing a language under the property testing approximation: it must distinguish inputs of the language from those that are eps-far from it, while using the smallest possible memory (rather than limiting its number of input queries). Our main result is a streaming eps-property tester for visibly pushdown languages (V_{PL}) with memory space poly(log n /epsilon). Our construction is done in three steps. First, we simulate a visibly pushdown automaton in one pass using a stack of small height but whose items can be of linear size. In a second step, those items are replaced by small sketches. Those sketches rely on a notion of suffix-sampling we introduce. This sampling is the key idea for taking benefit of both streaming algorithms and property testers in the third step. Indeed, the last step relies on a (non-streaming) property tester for weighted regular languages based on a previous tester by Alon et al. This tester can directly be used for streaming testing special cases of instances of V_{PL} that are already hard for both streaming algorithms and property testers. We then use it to decide the correctness of completed items, given their sketches, before removing them from the stack

Baroreceptors in the Aortic Arch and Their Potential Role in Aortic Dissection and Aneurysms

The arterial baroreflex is a key autonomic regulator of blood pressure whose dysfunction has been related to several cardiovascular diseases. Changes in blood pressure are sensed by specific mechanosensory proteins, called baroreceptors, particularly located in the outer layer of the carotid sinus and the inner curvature of the aortic arch. The signal is propagated along the afferent nerves to the central nervous system and serves as negative feedback of the heart rate. Despite extensive research, the precise molecular nature of baroreceptors remains elusive. Current knowledge assumes that baroreceptors are ion channels at the nerve endings within the outer layer of the arteries. However, the evidence is based mainly on animal experiments, and the specific types of mechanosensitive receptors responsible for the signal transduction are still unknown. Only a few studies have investigated mechanosensory transmission in the aortic arch. In addition, although aortic dissection, and particularly type A involving the aortic arch, is one of the most life-threatening cardiovascular disorders, there is no knowledge about the impact of aortic dissection on baroreceptor function. In this review, we aim not to highlight the regulation of the heart rate but what mechanical stimuli and what possible ion channels transfer the corresponding signal within the aortic arch, summarizing and updating the current knowledge about baroreceptors, specifically in the aortic arch, and the impact of aortic pathologies on their function

Kidney Retransplantation after Graft Failure: Variables Influencing Long-Term Survival

Background: There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective: To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan-Meier method, and risk factors were identified using multiple Cox regression. Results: We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, p=0.104) but an inferior graft survival thereafter (log-rank p=0.026). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson-Deyo index, active smoking, and life-threatening complications (Clavien-Dindo grade IV) at first transplantation. Conclusion: Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible

Sleeve Gastrectomy Enables Simultaneous Pancreas and Kidney Transplantation in Severely Obese Recipients

Background Obesity adversely affects wait‐listing and precludes patients with concomitant end‐stage renal disease and type 1 diabetes mellitus from getting a simultaneous pancreas and kidney transplantation (SPK). Objective To analyze safety and efficacy of laparoscopic sleeve gastrectomy (LSG) before SPK in severely obese type I diabetics. Methods We assessed weight curve, complications, and graft function of three patients who underwent LSG before SPK. Results LSG was uneventful in all patients. Body mass index dropped from 38.4 (range 35.7 ‐ 39.9) before LSG to 28.5 (26.8 ‐ 30.9) until SPK, with a mean loss of 25.8% (22.4 ‐ 32.3). Interval between LSG and SPK was 364.3 (173 ‐ 587) days. Pancreas and kidney graft function was excellent, with 100% insulin‐free and dialysis‐free survival over a mean follow‐up of 3.6 (2.9 ‐ 4.5) years. A1C dropped from 7% (6.3 ‐ 8.2) before LSG to 4.9% (4.7 ‐ 5.3) and 4.8% (4.5 ‐ 5.1) 1 and 2 years after SPK, respectively. Conclusion LSG before SPK is safe and effective to enable severely obese type I diabetics to receive a lifesaving transplant. This is the first study analyzing the role of bariatric surgery before simultaneous pancreas and kidney transplantation

The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study.

Background Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM). Methods We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls. Results Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR. Conclusion Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA

The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study

Background Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM). Methods We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls. Results Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR. Conclusion Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9-20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty®), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846). Keywords: COVID - 19; chimerism; hematopoietic stem cell transplantation (HSCT); immunocompetence; kidney transplantation; toleranc

Complication rates of peripherally inserted central catheters vs implanted ports in patients receiving systemic anticancer therapy: A retrospective cohort study

While implanted port catheters ("PORTs") have historically been the standard device for intravenous systemic anticancer therapy, the use of peripherally inserted central catheters (PICCs) has increased continuously and reliable catheter selection guidelines are lacking. We compare complication rates of PORTs and PICCs in cancer treatment in a retrospective study of 3365 patients with both solid organ (n = 2612) and hematologic (n = 753) malignancies, between 2001 and 2021. 26.4% (n = 890) of all patients were treated via PICCs and 73.6% (2475) via PORTs. 20.7% (578) experienced a major catheter-related complication with a higher rate in PICCs than in PORTs (23.5% vs 14.9%, P < .001). Among major complications, infections and mechanical complications were more common in PICCs than in PORTs (11.9% vs 6.4%, P = .001, 7.3% vs 4.2%, P = .002), whereas the rate of thrombosis was similar (3.4% vs 3.0%, P = .9). While PORTs had a higher rate of periprocedural complications (2.7% vs 1.1%, P < .05), PICCs overall complication rate exceeded PORTs within 3 days from implantation. Median follow-up was 49 (PICC) and 60 weeks (PORT). PORTs are safer and therefore should be preferred in this setting regardless of catheter dwell time

Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation – data from the Swiss transplant cohort study

BackgroundLiving donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants.MethodsWe investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants.ResultsWe found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss.ConclusionThe presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status