Blinatumomab consolidation post-autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771

An open toolkit for tracking open science partnership implementation and impact.

Serious concerns about the way research is organized collectively are increasingly being raised. They include the escalating costs of research and lower research productivity, low public trust in researchers to report the truth, lack of diversity, poor community engagement, ethical concerns over research practices, and irreproducibility. Open science (OS) collaborations comprise of a set of practices including open access publication, open data sharing and the absence of restrictive intellectual property rights with which institutions, firms, governments and communities are experimenting in order to overcome these concerns. We gathered two groups of international representatives from a large variety of stakeholders to construct a toolkit to guide and facilitate data collection about OS and non-OS collaborations. Ultimately, the toolkit will be used to assess and study the impact of OS collaborations on research and innovation. The toolkit contains the following four elements: 1) an annual report form of quantitative data to be completed by OS partnership administrators; 2) a series of semi-structured interview guides of stakeholders; 3) a survey form of participants in OS collaborations; and 4) a set of other quantitative measures best collected by other organizations, such as research foundations and governmental or intergovernmental agencies. We opened our toolkit to community comment and input. We present the resulting toolkit for use by government and philanthropic grantors, institutions, researchers and community organizations with the aim of measuring the implementation and impact of OS partnership across these organizations. We invite these and other stakeholders to not only measure, but to share the resulting data so that social scientists and policy makers can analyse the data across projects

High-performance computing and its applications to atomic structure physics

Modern atomic physics is increasingly dependent on the results of high-precision calculations to guide experiments and applications, especially in complex atoms with dense spectra. Many cutting-edge applications and experiments use atoms with open-shell electronic structure and strong configuration mixing, which require extremely large numerical bases to treat with any level of accuracy. At the same time, supercomputing clusters have seen huge increases in computational power, driven by increasingly large-scale parallelism across many distributed compute nodes. Consequently, modern atomic structure code must be designed to fully utilise massively-parallel computing resources if they are to keep up with the increasing demands of experimental studies.In this thesis, I present the results of work to modernise the AMBiT atomic structure software, which implements the configuration interaction with many-body perturbation theory (CI+MBPT) method, to take advantage of modern supercomputers. I present a detailed outline of the software engineering processes in converting AMBiT from an MPI-only model of parallelism to a hybrid MPI+OpenMP model, as well as the performance gains resulting from doing so. I show that the increased parallelism allows us to explore numerical saturation of the CI+MBPT method in open-shell atoms for the first time ever --- an investigation would not have been possible without the increased performance capabilities of modern supercomputers.I have applied the new AMBiT to calculations of atomic systems with a variety of electronic structures. Calculations of the highly-charged ions Sn7+-Sn10+, which are of experimental interest for their applications in extreme ultraviolet photolithography for semiconductor fabrication, show that AMBiT is highly efficient for ions with open d-shells. We achieve very close agreement with experimental spectra: CI+MBPT calculations differ from experiments by an average error of less than 1%. Additionally, calculations for two- and three-valent Lr+ and Lr demonstrate that CI+MBPT implemented in AMBiT can accurately calculate the spectra of superheavy elements - systems in which relativistic and QED effects are significant. My calculations for Lr and Lr+ also show that our CI+MBPT implementation is competitive with other cutting-edge methods for relativistic atomic structure calculations.This research shows that the accuracy of the CI+MBPT method, when scaled out to numerical saturation, is competitive with best-in-class methods for atomic structure calculations and can continue to serve as a workhorse for next-generation atomic structure calculations. Following its release, AMBiT has been used by multiple research groups for calculations of highly-charged ion clocks and precision tests for physics beyond the standard model. Furthermore, this research should put AMBiT and CI+MBPT in a strong position to scale up and capitalise on future gains in high-performance computing technology

Colour Diffusion implementation in CP2K

Source code and an example for non-equilibrium molecular dynamics with CP2K, instructions for compiling the cod

A qualitative exploration of online forums to support resilience of rural young people in Australia

Introduction: Prevention and early intervention are crucial strategies for improving young people’s mental health and well-being. Building resilience is a key component of these strategies, especially among young individuals in rural areas who face well-documented mental health disparities. This study aimed to investigate how online mental health forums can contribute to enhancing individual resilience in young rural users.Methods: A sample of forum posts (n = 1,000) made by Australian rural users (18–25 years) on an online peer support mental health forum were qualitatively analyzed. The analysis was guided by themes derived from the literature on indicators of rural resilience.Results: Analysis of forum posts showed evidence of rural resilience in forum users. Online peer support forums offered a virtual space for individuals to establish social connections, experience a sense of belonging, share information, acquire knowledge, and offer mutual support. There were indications of increased self-efficacy among forum users, as they demonstrated their ability to implement strategies for better managing their mental health.Discussion: These findings significantly contribute to our understanding of how online forums can enhance resilience factors that are beneficial for young people living in rural communities. In the context of prevention and early intervention, this study illustrates the intricate connections between forum design and user activity with resilience outcomes, providing valuable insights into the underlying causal mechanisms. Consequently, it emphasizes the importance of incorporating such digital interventions as integral components of mental health service ecosystems

Bronchiolitis Simulation Module in the Pediatric Preclerkship Educational Exercises (PRECEDE) Curriculum

Introduction Acute bronchiolitis is a viral infection infecting 90% of children under the age of 2 years, with approximately 200,000 deaths per year. The current standard of care remains largely respiratory support and prevention. Therefore, understanding how to assess and escalate respiratory supportive care is paramount for health care providers taking care of children. Methods We used a high-fidelity simulator to simulate an infant with progressing respiratory distress in the setting of acute bronchiolitis. The participants were pediatric clerkship medical students during their preclerkship educational exercises (PRECEDE). The students were asked to evaluate and treat the simulated patient. After debriefing, the students repeated the simulation. We assessed both performances via a weighted checklist specifically developed for this case to measure team performance. Students also completed an overall course evaluation. Results Ninety out of 121 pediatric clerkship students were enrolled. Performance improved from 57% to 86% ( p < .05). Donning appropriate personal protection equipment was the most missed item both pre- and postdebriefing. Overall, the course was well liked and received. Participants requested more simulation opportunities within PRECEDE as well as a summary document to reinforce learning. Discussion Pediatric clerkship students improved their performance managing progressing respiratory distress due to acute bronchiolitis via a performance-based assessment tool with sound validity evidence. Improvements going forward include improving faculty diversity and offering more simulation opportunities

An open toolkit for tracking open science partnership implementation and impact.

Serious concerns about the way research is organized collectively are increasingly being raised. They include the escalating costs of research and lower research productivity, low public trust in researchers to report the truth, lack of diversity, poor community engagement, ethical concerns over research practices, and irreproducibility. Open science (OS) collaborations comprise of a set of practices including open access publication, open data sharing and the absence of restrictive intellectual property rights with which institutions, firms, governments and communities are experimenting in order to overcome these concerns. We gathered two groups of international representatives from a large variety of stakeholders to construct a toolkit to guide and facilitate data collection about OS and non-OS collaborations. Ultimately, the toolkit will be used to assess and study the impact of OS collaborations on research and innovation. The toolkit contains the following four elements: 1) an annual report form of quantitative data to be completed by OS partnership administrators; 2) a series of semi-structured interview guides of stakeholders; 3) a survey form of participants in OS collaborations; and 4) a set of other quantitative measures best collected by other organizations, such as research foundations and governmental or intergovernmental agencies. We opened our toolkit to community comment and input. We present the resulting toolkit for use by government and philanthropic grantors, institutions, researchers and community organizations with the aim of measuring the implementation and impact of OS partnership across these organizations. We invite these and other stakeholders to not only measure, but to share the resulting data so that social scientists and policy makers can analyse the data across projects

Multiple forest attributes underpin the supply of multiple ecosystem services

Trade-offs and synergies in the supply of forest ecosystem services are common but the drivers of these relationships are poorly understood. To guide management that seeks to promote multiple services, we investigated the relationships between 12 stand-level forest attributes, including structure, composition, heterogeneity and plant diversity, plus 4 environmental factors, and proxies for 14 ecosystem services in 150 temperate forest plots. Our results show that forest attributes are the best predictors of most ecosystem services and are also good predictors of several synergies and trade-offs between services. Environmental factors also play an important role, mostly in combination with forest attributes. Our study suggests that managing forests to increase structural heterogeneity, maintain large trees, and canopy gaps would promote the supply of multiple ecosystem services. These results highlight the potential for forest management to encourage multifunctional forests and suggest that a coordinated landscape-scale strategy could help to mitigate trade-offs in human-dominated landscapes