Investigation of implementing a synchronization protocol under multiprocessors hierarchical scheduling

In the multi-core and multiprocessor domain, there has been considerable work done on scheduling techniques assuming that real-time tasks are independent. In practice a typical real-time system usually share logical resources among tasks. However, synchronization in the multiprocessor area has not received enough attention. In this paper we investigate the possibilities of extending multiprocessor hierarchical scheduling to support an existing synchronization protocol (FMLP) in multiprocessor systems. We discuss problems regarding implementation of the synchronization protocol under the multiprocessor hierarchical scheduling

Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice

A murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-γ and TNF-α. Lethally irradiated (C57BL × CBA)F1 mice were reconstituted either with 107 allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-α and IFN-γ levels was found in allogeneically reconstituted mice. This is in contrast to the syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice IL-6, IFN-γ and TNF-α concentrations were increased. The expression of mRNA for cytokines as detected by reverse transcription PCR was studied in spleen cells. In the allogeneic reconstituted mice the mRNA expression of IL-1α, IL-2, IL-6, IFN-γ and TNF-α displayed faster kinetics compared with that in syngeneic reconstituted mice. The effect of treatment with recombinant cytokines, antibodies to cytokines and to cytokine receptors on the development of GVHD was investigated. Administration of recombinant IL-2 to allogeneically reconstituted mice strongly increased the morbidity and mortality whereas injection of IL-1α and TNF-α did not influence survival. Administration of antibodies against IL-2 or the IL-2 receptor decreased the morbidity and mortality. Anti-IL-6, anti-IFN-γ, and anti-TNF-α mAB, on the other hand, did not affect the morbidity and mortality of GVHD. The results of this study suggest successive waves of cytokine-secreting cell populations consistent with the induction of an inflammatory response in the development of acute GVH disease

Efficacy and safety of rozanolixizumab in moderate to severe generalized myasthenia gravis : a phase 2 randomized control trial

OBJECTIVE: To explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG). METHODS: In this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1-29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29-43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44-99). Primary endpoint was change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints were change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores and safety. RESULTS: Forty-three patients were randomized (rozanolixizumab 21, placebo 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo was as follows: QMG (LS mean -1.8 vs -1.2, difference -0.7, 95% upper confidence limit [UCL] 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean -1.8 vs -0.4, difference -1.4, 95% UCL -0.4), and MGC (LS mean -3.1 vs -1.2, difference -1.8, 95% UCL 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab 57%, placebo 14%). CONCLUSION: Whereas change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with gMG, rozanolixizumab is well-tolerated, but did not significantly improve QMG score

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Toward a Regulatory Pathway for the Use of in Silico Trials in The Ce Marking of Medical Devices

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing

Exact Speedup Factors and Sub-Optimality for Non-Preemptive Scheduling

Fixed priority scheduling is used in many real-time systems; however, both preemptive and non-preemptive variants (FP-P and FP-NP) are known to be sub-optimal when compared to an optimal uniprocessor scheduling algorithm such as preemptive earliest deadline first (EDF-P). In this paper, we investigate the sub-optimality of fixed priority non-preemptive scheduling. Specifically, we derive the exact processor speed-up factor required to guarantee the feasibility under FP-NP (i.e. schedulability assuming an optimal priority assignment) of any task set that is feasible under EDF-P. As a consequence of this work, we also derive a lower bound on the sub-optimality of non-preemptive EDF (EDF-NP). As this lower bound matches a recently published upper bound for the same quantity, it closes the exact sub-optimality for EDF-NP. It is known that neither preemptive, nor non-preemptive fixed priority scheduling dominates the other, in other words, there are task sets that are feasible on a processor of unit speed under FP-P that are not feasible under FP-NP and vice-versa. Hence comparing these two algorithms, there are non-trivial speedup factors in both directions. We derive the exact speed-up factor required to guarantee the FP-NP feasibility of any FP-P feasible task set. Further, we derive the exact speed-up factor required to guarantee FP-P feasibility of any constrained-deadline FP-NP feasible task set

Lymph Node Negative Colorectal Cancers with Isolated Tumor Deposits Should Be Classified and Treated As Stage III

BACKGROUND: The prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients. MATERIALS AND METHODS: The medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated. RESULTS: Disease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P <.01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present. CONCLUSIONS: Because of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considere

Methane retrievals from Greenhouse Gases Observing Satellite (GOSAT) shortwave infrared measurements: Performance comparison of proxy and physics retrieval algorithms

We compare two conceptually different methods for determining methane column-averaged mixing ratios image from Greenhouse Gases Observing Satellite (GOSAT) shortwave infrared (SWIR) measurements. These methods account differently for light scattering by aerosol and cirrus. The proxy method retrieves a CO_2 column which, in conjunction with prior knowledge on CO_2 acts as a proxy for scattering effects. The physics-based method accounts for scattering by retrieving three effective parameters of a scattering layer. Both retrievals are validated on a 19-month data set using ground-based X_CH_4 at 12 stations of the Total Carbon Column Observing Network (TCCON), showing comparable performance: for the proxy retrieval we find station-dependent retrieval biases from −0.312% to 0.421% of X_CH_4 a standard deviation of 0.22% and a typical precision of 17 ppb. The physics method shows biases between −0.836% and −0.081% with a standard deviation of 0.24% and a precision similar to the proxy method. Complementing this validation we compared both retrievals with simulated methane fields from a global chemistry-transport model. This identified shortcomings of both retrievals causing biases of up to 1ings and provide a satisfying validation of any methane retrieval from space-borne SWIR measurements, in our opinion it is essential to further expand the network of TCCON stations