Robustness Against Read Committed for Transaction Templates with Functional Constraints

The popular isolation level Multiversion Read Committed (RC) trades some of the strong guarantees of serializability for increased transaction throughput. Sometimes, transaction workloads can be safely executed under RC obtaining serializability at the lower cost of RC. Such workloads are said to be robust against RC. Previous work has yielded a tractable procedure for deciding robustness against RC for workloads generated by transaction programs modeled as transaction templates. An important insight of that work is that, by more accurately modeling transaction programs, we are able to recognize larger sets of workloads as robust. In this work, we increase the modeling power of transaction templates by extending them with functional constraints, which are useful for capturing data dependencies like foreign keys. We show that the incorporation of functional constraints can identify more workloads as robust that otherwise would not be. Even though we establish that the robustness problem becomes undecidable in its most general form, we show that various restrictions on functional constraints lead to decidable and even tractable fragments that can be used to model and test for robustness against RC for realistic scenarios

An Optimized Photon Pair Source for Quantum Circuits

We implement an ultrafast pulsed type-II parametric down conversion source in a periodically poled KTP waveguide at telecommunication wavelengths with almost identical properties between signal and idler. As such, our source resembles closely a pure, genuine single mode photon pair source with indistinguishable modes. We measure the joint spectral intensity distribution and second order correlation functions of the marginal beams and find with both methods very low effective mode numbers corresponding to a Schmidt number below 1.16. We further demonstrate the indistinguishability as well as the purity of signal and idler photons by Hong-Ou-Mandel interferences between signal and idler and between signal/idler and a coherent field, respectively. Without using narrowband spectral filtering, we achieve a visibility for the interference between signal and idler of 94.8% and determine a purity of more than 80% for the heralded single photon states. Moreover, we measure raw heralding efficiencies of 20.5% and 15.5% for the signal and idler beams corresponding to detector-loss corrected values of 80% and 70%.Comment: 11 pages, 8 figure

Robustness against Read Committed for Transaction Templates with Functional Constraints

The popular isolation level Multiversion Read Committed (RC) trades some of the strong guarantees of serializability for increased transaction throughput. Sometimes, transaction workloads can be safely executed under RC obtaining serializability at the lower cost of RC. Such workloads are said to be robust against RC. Previous work has yielded a tractable procedure for deciding robustness against RC for workloads generated by transaction programs modeled as transaction templates. An important insight of that work is that, by more accurately modeling transaction programs, we are able to recognize larger sets of workloads as robust. In this work, we increase the modeling power of transaction templates by extending them with functional constraints, which are useful for capturing data dependencies like foreign keys. We show that the incorporation of functional constraints can identify more workloads as robust that otherwise would not be. Even though we establish that the robustness problem becomes undecidable in its most general form, we show that various restrictions on functional constraints lead to decidable and even tractable fragments that can be used to model and test for robustness against RC for realistic scenarios

Adjuvant radiotherapy and chemoradiation with gemcitabine after R1 resection in patients with pancreatic adenocarcinoma

Background: The purpose of the study was to evaluate the effect of radiation therapy and chemoradiation with gemcitabine (GEM) after R1 resection in patients with pancreatic adenocarcinoma (PAC). Methods: We performed a retrospective analysis of 25 patients who were treated with postoperative radiotherapy (RT) or chemoradiation (CRT) after surgery with microscopically positive resection margins for primary pancreatic cancer (PAC). Median age was 60 years (range 34 to 74 years), and there were 17 male and 8 female patients. Fractionated RT was applied with a median dose of 49.6 Gy (range 36 to 54 Gy). Eight patients received additional intraoperative radiotherapy (IORT) with a median dose of 12 Gy. Results: Median overall survival (mOS) of all treated patients was 22 months (95% confidence interval (CI) 7.9 to 36.1 months) after date of resection and 21.1 months (95% CI 7.6 to 34.6 months) after start of (C)RT. Median progression-free survival (mPFS) was 13.0 months (95% CI 0.93 to 25 months). Grading (G2 vs. G3, P = 0.005) and gender (female vs. male, P = 0.01) were significantly correlated with OS. There was a significant difference in mPFS between male and female patients (P = 0.008). A total of 11 from 25 patients experienced local tumour progression, and 19 patients were diagnosed with either locoregional or distant failure. Conclusions: We demonstrated that GEM-based CRT can be applied in analogy to neoadjuvant protocols in the adjuvant setting for PAC patients at high risk for disease recurrence after incomplete resection. Patients undergoing additive CRT have a rather good OS and PFS compared to historical control patient groups

Outcome for pediatric adreno-cortical tumors is best predicted by the COG stage and five-item microscopic score — report from the German MET studies

Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score. Results: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1–17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0–16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS. Conclusions: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score

Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia

We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n = 23) or mixed chimerism (MC, n = 169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n = 126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II–IV°/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ≥60 years (p = 0.046), advanced stage at transplantation (p = 0.003), shorter interval from transplantation (p = 0.018), and prior aGvHD ≥II° (p = 0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD

Adjuvant therapy for children treated by enucleation at diagnosis of retinoblastoma

Introduction Advanced localized retinoblastoma can be cured by enucleation, but extraocular spread of retinoblastoma cells is associated with a high mortality. Risk-stratified adjuvant treatment with chemotherapy and radiotherapy has been shown to reduce the risk for extraocular relapse in children with histopathological risk factors. Methods Data of 184 patients with retinoblastoma and primary enucleation were collected in a prospective, multicenter, observational study between 2013 and 2020. The clinical characteristics were evaluated as risk factors and progression-free and overall survival rates were compared. Results Seventy-one percent of 184 children with retinoblastoma treated with primary enucleation were diagnosed with low risk histopathological factors (pT1/pT2a) and received no adjuvant therapy. Children with intermediate risk (pT2b,pT3; 48 children, 26.0%) and high risk for metastasis (pT4; 5 children, 2.7%) received risk-stratified adjuvant treatment. None of the children with low risk or intermediate risk (pT1-pT3) relapsed, but two of five children with high-risk retinoblastoma (pT4) developed extraocular relapses and one deceased. The 2-year progression-free survival rate and 2-year overall survival rate was 100% for children with pT1-3 retinoblastoma. However, the 2-year progression-free survival rate and 2-year overall survival rate for children with pT4 was statistically notably reduced with 2 of 5 children developing progression and 1 death among the 5 children within 2 years after diagnosis. Conclusion Primary enucleation alone and with additional risk-stratified adjuvant chemotherapy treatment provides high cure rates in patients with pT1-3 retinoblastoma, but children with pT4 retinoblastoma remain at high risk to develop extraocular retinoblastoma. International prospective clinical trials are required to evaluate reduction of intensity of adjuvant chemotherapy in some risk groups (pT2, pT3) and intensification for pT4 retinoblastoma

JNK Isoforms Differentially Regulate Neurite Growth and Regeneration in Dopaminergic Neurons In Vitro

Parkinson’s disease is characterized by selective and progressive loss of midbrain DAergic neurons (MDN) in the substantia nigra and degeneration of its nigrostriatal projections. Whereas the cellular pathophysiology has been closely linked to an activation of c-Jun N-terminal kinases (JNKs) and c-Jun, the involvement of JNKs in regenerative processes of the nigrostriatal pathway is controversially discussed. In our study, we utilized a mechanical scratch lesion paradigm of midbrain DAergic neurons in vitro and studied regenerative neuritic outgrowth. After a siRNA-mediated knockdown of each of the three JNK isoforms, we found that JNKs differentially regulate neurite regeneration. Knockdown of JNK3 resulted in the most prominent neurite outgrowth impairment. This effect was attenuated again by plasmid overexpression of JNK3. We also evaluated cell survival of the affected neurons at the scratch border. JNK3 was found to be also relevant for survival of MDN which were lesioned by the scratch. Our data suggest that JNK isoforms are involved in differential regulation of cell death and regeneration in MDN depending on their neurite integrity. JNK3 appears to be required for regeneration and survival in the case of an environment permissive for regeneration. Future therapeutic approaches for the DAergic system may thus require isoform specific targeting of these kinases