On-the-fly memory compression for multibody algorithms.

Memory and bandwidth demands challenge developers of particle-based codes that have to scale on new architectures, as the growth of concurrency outperforms improvements in memory access facilities, as the memory per core tends to stagnate, and as communication networks cannot increase bandwidth arbitrary. We propose to analyse each particle of such a code to find out whether a hierarchical data representation storing data with reduced precision caps the memory demands without exceeding given error bounds. For admissible candidates, we perform this compression and thus reduce the pressure on the memory subsystem, lower the total memory footprint and reduce the data to be exchanged via MPI. Notably, our analysis and transformation changes the data compression dynamically, i.e. the choice of data format follows the solution characteristics, and it does not require us to alter the core simulation code

Critical care triage during the COVID-19 pandemic in South Africa: A constitutional imperative!

Triage and rationing of scarce intensive care unit (ICU) resources are an unavoidable necessity. In routine circumstances, ICU triage is premised on the best interests of an individual patient; however, when increased demand exceeds capacity, as during an infectious disease outbreak, healthcare providers need to make difficult decisions to benefit the broader community while still respecting individual interests. We are currently living through an unprecedented period, with South Africa (SA) facing the challenges of the global COVID-19 pandemic. The Critical Care Society of Southern Africa (CCSSA) expedited the development of a triage guidance document to inform the appropriate and fair use of scarce ICU resources during this pandemic. Triage decision-making is based on the clinical odds of a positive ICU outcome, balanced against the risk of mortality and longer-term morbidity affecting quality of life. Factors such as age and comorbid conditions are considered for their potential impact on clinical outcome, but are never the sole criteria for denying ICU-level care. Arbitrary, unfair discrimination is never condoned. The CCSSA COVID-19 triage guideline is aligned with SA law and international ethical standards, and upholds respect for all persons. The Bill of Rights, however, does not mandate the level of care enshrined in the constitutional right to healthcare. ICU admission is not always appropriate, available or feasible for every person suffering critical illness or injury; however, everyone has the right to receive appropriate healthcare at another level. If ICU resources are used for people who do not stand to benefit, this effectively denies others access to potentially life-saving healthcare. Appropriate triaging can therefore be considered a constitutional imperative

Aquatic Treadmill Training Reduces Blood Pressure Reactivity to Acute Graded Exercise in Previously Sedentary Adults

Endurance exercise may reduce blood pressure and improve vasodilatory capacity thereby blunting the hypertensive response to stress. To test the efficacy of a novel model of low-impact endurance training, the aquatic-based treadmill (ATM), to improve blood pressure parameters, we recruited 60 sedentary adults and randomized to 12-weeks of either ATM (n = 36 [19 men, 17 women] , 41±2 yr, 173.58 ±1.58cm, 93.19 ±3.15kg) or land-based treadmill (LTM, n = 24 [11 men, 13 women], 42 ±2yr, 170.39 ±1.94cm, 88.14 ±3.6kg) training; 3sessions·wk-1, progressing to 500 kcal·session-1, 85% VO2max. The maximal Bruce treadmill test protocol was performed before and after training with blood pressures measured prior to, at the end of each stage, and for 5 minutes following exercise testing. Twelve subjects (5 ATM, 7 LTM) volunteered for biopsies of the vastus lateralis before and after training, and muscle samples were assessed for eNOS content. Blood pressure data were analyzed using group by training ANCOVA repeated across training, α = 0.05. Data obtained from muscle sample analysis were analyzed using group by training ANOVA repeated across training α = 0.05. Training reduced systolic blood pressure (9- 18.2mmHg), diastolic blood pressure (3.2-8.1 mmHg), mean arterial pressure (4.8-8.3mmHg), pulse pressure (7.5-15mmHg), and rate pressure product (1.8-3.9 bpm·mm Hg·103) during exercise stress and recovery in the ATM group, but not in the LTM group. Additionally, the ATM group, but not the LTM group, displayed a 31% increase in skeletal muscle eNOS content following training. Both groups improved VO2max (+3.6mL O2·kg-1·min-1), but resting blood pressure was not changed following training. These data support the use of ATM training as a novel therapeutic modality to combat hypertension

On-the-fly memory compression for multibody algorithms

Memory and bandwidth demands challenge developers of particle-based codes that have to scale on new architectures, as the growth of concurrency outperforms improvements in memory access facilities, as the memory per core tends to stagnate, and as communication networks cannot increase bandwidth arbitrary. We propose to analyse each particle of such a code to find out whether a hierarchical data representation storing data with reduced precision caps the memory demands without exceeding given error bounds. For admissible candidates, we perform this compression and thus reduce the pressure on the memory subsystem, lower the total memory footprint and reduce the data to be exchanged via MPI. Notably, our analysis and transformation changes the data compression dynamically, i.e. the choice of data format follows the solution characteristics, and it does not require us to alter the core simulation code

Nuclear structure and reaction studies at SPIRAL

The SPIRAL facility at GANIL, operational since 2001, is described briefly. The diverse physics program using the re-accelerated (1.2 to 25 MeV/u) beams ranging from He to Kr and the instrumentation specially developed for their exploitation are presented. Results of these studies, using both direct and compound processes, addressing various questions related to the existence of exotic states of nuclear matter, evolution of new "magic numbers", tunnelling of exotic nuclei, neutron correlations, exotic pathways in astrophysical sites and characterization of the continuum are discussed. The future prospects for the facility and the path towards SPIRAL2, a next generation ISOL facility, are also briefly presented.Comment: 48 pages, 27 figures. Accepted for publication in Journal of Physics

HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast

Abstract Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors