Topology-aware Quality-of-Service Support in Highly Integrated Chip Multiprocessors

Current design complexity trends, poor wire scalability, and power limitations argue in favor of highly modular onchip systems. Today’s state-of-the-art CMPs already feature up to a hundred discrete cores. With increasing levels of integration, CMPs with hundreds of cores, cache tiles, and specialized accelerators are anticipated in the near future. Meanwhile, server consolidation and cloud computing paradigms have emerged as profit vehicles for exploiting abundant resources of chip-multiprocessors. As multiple, potentially malevolent, users begin to share virtualized resources of a single chip, CMP-level quality-of-service (QOS) support becomes necessary to provide performance isolation, service guarantees, and security. This work takes a topology-aware approach to on-chip QOS. We propose to segregate shared resources, such as memory controllers and accelerators, into dedicated islands (shared regions) of the chip with full hardware QOS support. We rely on a richly connected Multidrop Express Channel (MECS) topology to connect individual nodes to shared regions, foregoing QOS support in much of the substrate and eliminating its respective overheads. We evaluate several topologies for the QOSenabled shared regions, focusing on the interaction between network-on-chip (NOC) and QOS metrics. We explore a new topology called Destination Partitioned Subnets (DPS), which uses a light-weight dedicated network for each destination node. On synthetic workloads, DPS nearly matches or outperforms other topologies with comparable bisection bandwidth in terms of performance, area overhead, energyefficiency, fairness, and preemption resilience.

Improvement of physicochemical parameters of acyclovir using cocrystallization approach

ABSTRACT Acyclovir is an antiviral drug having potent activity against the virus of herpes family and varicella zoster. Unfortunately, drug suffers very poor oral bioavailability (15-30%). The main objective of present study was to develop acyclovir cocrystals with improved solubility which may result in improvement of bioavailability. Hansen solubility approach was used as a tool to predict the cocrystal formation of a drug with selected coformer. Cocrystals of acyclovir with various coformers were screened in order to enhance their water solubility. Cocrystals of the drug were prepared using various methods like solvent evaporation, wet grinding, and antisolvent addition. Formation of cocrystals by solvent evaporation method was found to be better method amongst all. Optimization of cocrystal formation was carried out by employing different solvents as well as the stoichiometric ratio of acyclovir with that of coformer. Synthesis of cocrystals was optimized using water as a solvent system resulted in good agreements. The potential cocrystal formation of acyclovir was characterized by IR, PXRD and DSC techniques. An in-vitro dissolution study was performed to determine the dissolution rate of cocrystals. The results suggest that acyclovir forms cocrystals with tartaric acid and the initial dissolution rate of synthesized cocrystals were considerably faster as compared to pure acyclovir

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Ecology and Control of an Introduced Population of Southern Watersnakes ( Nerodia fasciata

Native to the southeastern United States, Southern Watersnakes (Nerodia fasciata) are known from two sites in California, but their ecological impacts are poorly understood. We investigated the ecology of Southern Watersnakes in Machado Lake, Harbor City, Los Angeles County, California, including an assessment of control opportunities. We captured 306 watersnakes as a result of aquatic trapping and hand captures. We captured snakes of all sizes (162-1063 mm snout-vent length [SVL], 3.5-873.3 g), demonstrating the existence of a well-established population. The smallest reproductive female was 490 mm SVL and females contained 12-46 postovulatory embryos (mean = 21). Small watersnakes largely consumed introduced Western Mosquitofish (Gambusia affinis), while larger snakes specialized on larval and metamorph American Bullfrogs (Lithobates catesbeianus) and Green Sunfish (Lepomis cyanellus). Overall capture per unit effort (CPUE) in traps declined with time during an intensive 76-d trapping bout, but CPUE trends varied considerably among traplines and it is unlikely that the overall decline in CPUE represented a major decrease in the snake population size. Although we found no direct evidence that Southern Watersnakes are affecting native species in Machado Lake, this population may serve as a source for intentional or unintentional transportation of watersnakes to bodies of water containing imperiled native prey species or potential competitors