Elasto-plastic impact of hemispherical shell impacting on hard rigid sphere

An analysis of plastic stress waves for cylindrical metallic projectile in impact is extended to an analysis of a hemispherical shell suffereing plastic deformation during the process of impact. It is assumed that the hemispherical shell with a prescribed launch velocity impinges a fixed rigid sphere of diameter equal to the internal diameter of the shell. The dynamic biaxial state of stress present in the shell during deformation is investigated. The analysis is valuable for studying the state of stress during large plastic deformation of a hemispherical shell

Application of boundary integral method to elastoplastic analysis of V-notched beams

The boundary integral equation method was applied in the solution of the plane elastoplastic problem. The use of this method was illustrated by obtaining stress and strain distributions for a number of specimens with a single-edge notch and subjected to pure bending. The boundary integral equation method reduced the inhomogeneous biharmonic equation to two coupled Fredholm-type integral equations. These integral equations were replaced by a system of simultaneous algebraic equations and solved numerically in conjunction with a method of successive elastic solutions

Experimental and numerical study of error fields in the CNT stellarator

Sources of error fields were indirectly inferred in a stellarator by reconciling computed and numerical flux surfaces. Sources considered so far include the displacements and tilts (but not the deformations, yet) of the four circular coils featured in the simple CNT stellarator. The flux surfaces were measured by means of an electron beam and phosphor rod, and were computed by means of a Biot-Savart field-line tracing code. If the ideal coil locations and orientations are used in the computation, agreement with measurements is poor. Discrepancies are ascribed to errors in the positioning and orientation of the in-vessel interlocked coils. To that end, an iterative numerical method was developed. A Newton-Raphson algorithm searches for the coils' displacements and tilts that minimize the discrepancy between the measured and computed flux surfaces. This method was verified by misplacing and tilting the coils in a numerical model of CNT, calculating the flux surfaces that they generated, and testing the algorithm's ability to deduce the coils' displacements and tilts. Subsequently, the numerical method was applied to the experimental data, arriving at a set of coil displacements whose resulting field errors exhibited significantly improved quantitative and qualitative agreement with experimental results.Comment: Special Issue on the 20th International Stellarator-Heliotron Worksho

Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies

PURPOSE: Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. METHODS: In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) increase of \u3e/=1 g/dL from baseline. RESULTS: Both studies were terminated early due to slow patient accrual. Among patients treated with sotatercept in the A011-08 and ACE-011-NSCL-001 studies, more patients achieved a mean Hb increase of \u3e/=1 g/dL in the combined sotatercept 0.3 mg/kg and 15 mg (66.7 %) group and sotatercept 0.5 mg/kg and 30 mg (38.9 %) group versus the sotatercept 0.1 mg/kg (0 %) group. No patients achieved a mean Hb increase of \u3e/=1 g/dL in the placebo group. The incidence of treatment-related adverse events (AEs) was low in both studies, and treatment discontinuations due to AEs were uncommon. CONCLUSIONS: Although both studies were terminated early, these results indicate that sotatercept is active and has an acceptable safety profile in the treatment of CIA

Zimbabwe’s land reform: challenging the myths

Most commentary on Zimbabwe’s land reform insists that agricultural production has almost totally collapsed, that food insecurity is rife, that rural economies are in precipitous decline, that political ‘cronies’ have taken over the land and that farm labour has all been displaced. This paper however argues that the story is not simply one of collapse and catastrophe; it is much more nuanced and complex, with successes as well as failures. The paper provides a summary of some of the key findings from a ten-year study in Masvingo province and the book Zimbabwe’s Land Reform: Myths and Realities. The paper documents the nature of the radical transformation of agrarian structure that has occurred both nationally and within the province, and the implications for agricultural production and livelihoods. A discussion of who got the land shows the diversity of new settlers, many of whom have invested substantially in their new farms. An emergent group ‘middle farmers’ is identified who are producing, investing and accumulating. This has important implications – both economically and politically – for the future, as the final section on policy challenges discusses.ESR

Pembrolizumab in Combination with Ipilimumab as Second-Line or Later Therapy for Advanced Non–Small-Cell Lung Cancer: KEYNOTE-021 Cohorts D and H

Objectives Combination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy with anti‒programmed death 1 (PD-1) antibody pembrolizumab plus anti‒cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in patients with previously treated advanced non–small-cell lung cancer (NSCLC). Materials and Methods Eligibility criteria stipulated histologically/cytologically confirmed advanced NSCLC and treatment failure on ≥1 prior systemic therapy (platinum-based chemotherapy or targeted therapy for patients with EGFR/ALK aberrations). In the dose-finding cohort, patients initially received pembrolizumab 10 mg/kg plus ipilimumab 1 or 3 mg/kg once every 3 weeks for 4 cycles followed by pembrolizumab 10 mg/kg monotherapy for up to 2 years. Based on emerging published data, subsequent patients received pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg. Objective response rate (ORR; primary efficacy endpoint) was assessed per RECIST version 1.1 by blinded, independent central review. Phase 2 hypothesis that ORR would be greater than the 20% rate for historical controls was evaluated using the exact binomial test. Results Fifty-one patients were enrolled; 71% received ≥2 prior lines of therapy. No dose-limiting toxicities occurred at any dose level. Among patients who received pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg (n = 44), ORR was 30% (95% CI, 17%–45%), but not statistically significantly >20% (P = 0.0858). Median progression-free survival in this group was 4.1 (95% CI, 1.4–5.8) months; median overall survival was 10.9 (95% CI, 6.1–23.7) months. With pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg, incidences of treatment-related adverse events, grade 3–5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions were 64%, 29% and 42%, respectively. Conclusions In patients with heavily pretreated advanced NSCLC, pembrolizumab plus ipilimumab showed evidence of antitumor activity, but was associated with meaningful toxicity

DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma

DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma