A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement

CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement

Mental disorders and work integration: a retrospective study in a northern italian town.

OBJECTIVES: THE PRESENT STUDY WAS CONDUCTED IN A VOCATIONAL INTEGRATION SERVICE OF A NORTHERN ITALIAN TOWN WITH TWO MAJOR AIMS: to assess vocational integration programs undertaken from 1(st) January 2004 to 1(st) January 2007; and to identify job tenure-associated predictors. METHODS: This is a retrospective study; we collected data such as gender, age, duration, type and outcome of the vocational integration program, and number of interventions performed by the vocational integration service. Self-report questionnaires were also used to assess the satisfaction of users, caregivers, practitioners, and of the company contacts involved in the study. RESULTS: The service has enrolled 84 users during the observation period. Out of these users, 64.3% of them still had their jobs after three years. Users, caregivers and company contacts expressed high levels of satisfaction for the support received by the vocational integration service. The company expressed less satisfaction for the collaboration received by the Departments of Mental Health (DMHs) that coached the users. The only variable associated to the outcome was the number of interventions that the users received before their placement on the job. CONCLUSIONS: Despite all the limits of this study, its results show that the chance of taking advantage of a supported job placement service has likely proven itself effective in helping people with mental disorders to obtain and maintain a competitive employment. Our results, however, also point to the necessity of implementing newer strategies meant to develop a greater integration among all services dealing with mentally ill people

An 81-Year-Old Man with a 6-Year History of Chronic Lymphocytic Leukemia Presenting with Disease Flare Following Ibrutinib Discontinuation

Patient: Male, 81-year-old Final Diagnosis: Chronic lymphocytic leukemia Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Hematology Objective: Background: Case Report: Conclusions: Unusual clinical course Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm and the most common leukemia in adults in Western countries. Novel agents, including BTK inhibitors and the BCL2 inhibitor venetoclax, have dramati-cally changed the treatment landscape. Moreover, a disease flare, characterized by sudden worsening of clinical symptoms, radiographic findings of rapidly worsening splenomegaly or lymphadenopathy, and laboratory changes (increased absolute lymphocyte count or lactate dehydrogenase), is a phenomenon described in up to 25% of patients with CLL after ibrutinib discontinuation. We describe a patient with CLL with disease flare after ibrutinib discontinuation due to disease progression and describe the subsequent management of vene-toclax initial treatment in the course of the disease flare. We describe the case of an 81-year-old man with a 6-year history of CLL who was treated with multiple lines of therapy and developed worsening of disease-related signs and symptoms with fever, marked increase of lym-phocyte count, acute worsening of renal function, and increase in lymph nodes and spleen size following ces-sation of targeted therapy with ibrutinib at the time of disease progression. There was subsequent overlap-ping of ibrutinib during the venetoclax dose escalation period to prevent disease flare recurrence. Our report highlights the problem of disease flare after ibrutinib discontinuation in order to avoid associated patient morbidity, underscoring the importance of awareness of this phenomenon and focusing on the addition of venetoclax at time of progression in ibrutinib-treated patients, as a temporary overlap strategy, to prevent disease flare

The machine protection system for the ELI-NP gamma beam system

The new Gamma Beam System (GBS) of the ELI-NPproject [1], currently under installation in Magurele (RO)by INFN, as part of EuroGammas consortium, can providegamma rays that open new possibilities for nuclear photonicsand nuclear physics.ELI-NP gamma rays are produced by Compton back-scattering to get monochromaticity (0,1% bandwidth), highflux (1013photons), tunable direction and energy up to19.5 MeV. Such gamma beam is obtained when a high-intensity laser collides a high-brightness electron beam withenergies up to740 MeV, a repetition rate of100 Hz, withtrains of 32 bunches within the same RF bucket.An advanced Machine Protection System (MPS) has beendeveloped, in order to ensure proper operation for this chal-lenging facility. The MPS operates on different layers of thecontrol system and is interfaced with all its sub-systems. Forinstance, it comprises different kind of beam loss monitors(based on Cherenkov optical fiber), hall probes, fast currenttransformer together with BPMs, and an embedded systembased on FPGA with distributed I/O over EtherCAT, to mon-itor vacuum and RF systems [2], which require fast responseto be interlocked within one RF pulse

A surge in obsidian exploitation more than 1.2 million years ago at Simbiro III (Melka Kunture, Upper Awash, Ethiopia)

Pleistocene archaeology records the changing behaviour and capacities of early hominins. These behavioural changes, for example, to stone tools, are commonly linked to environmental constraints. It has been argued that, in earlier times, multiple activities of everyday life were all uniformly conducted at the same spot. The separation of focused activities across different localities, which indicates a degree of planning, according to this mindset characterizes later hominins since only 500,000 years ago. Simbiro III level C, in the upper Awash valley of Ethiopia, allows us to test this assumption in its assemblage of stone tools made only with obsidian, dated to more than 1.2 million years (Myr) old. Here we first reconstruct the palaeoenvironment, showing that the landscape was seasonally flooded. Following the deposition of an accumulation of obsidian cobbles by a meandering river, hominins began to exploit these in new ways, producing large tools with sharp cutting edges. We show through statistical analysis that this was a focused activity, that very standardized handaxes were produced and that this was a stone-tool workshop. We argue that at Simbiro III, hominins were doing much more than simply reacting to environmental changes; they were taking advantage of new opportunities, and developing new techniques and new skills according to them