Random Scheduling Research Articles

Scheduling strategies for the ESPRESSO follow-up of TESS targets

ABSTRACT Radial-velocity follow-up of stars harbouring transiting planets detected by TESS is expected to require very large amounts of expensive telescope time in the next few years. Therefore, scheduling strategies should be implemented to maximize the amount of information gathered about the target planetary systems. We consider myopic and non-myopic versions of a novel uniform-in-phase scheduler, as well as a random scheduler, and compare these scheduling strategies with respect to the bias, accuracy and precision achieved in recovering the mass and orbital parameters of transiting and non-transiting planets. This comparison is carried out based on realistic simulations of radial-velocity follow-up with ESPRESSO of a sample of 50 TESS target stars, with simulated planetary systems containing at least one transiting planet with a radius below 4R⊕. Radial-velocity data sets were generated under reasonable assumptions about their noise component, including that resulting from stellar activity, and analysed using a fully Bayesian methodology. We find the random scheduler leads to a more biased, less accurate, and less precise, estimation of the mass of the transiting exoplanets. No significant differences are found between the results of the myopic and non-myopic implementations of the uniform-in-phase scheduler. With only about 22 radial velocity measurements per data set, our novel uniform-in-phase scheduler enables an unbiased (at the level of 1 per cent) measurement of the masses of the transiting planets, while keeping the average relative accuracy and precision around 16 per cent and 23 per cent, respectively. The number of non-transiting planets detected is similar for all the scheduling strategies considered, as well as the bias, accuracy and precision with which their masses and orbital parameters are recovered.

Replication and data management-based workflow scheduling algorithm for multi-cloud data centre platform

Scientific workflow applications have a large amount of tasks and data sets to be processed in a systematic manner. These applications benefit from cloud computing platform that offer access to virtually limitless resources provisioned elastically and on demand. Running data-intensive scientific workflow on geographically distributed data centres faces massive amount of data transfer. That affects the whole execution time and monitory cost of scientific workflows. The existing efforts on scheduling workflow concentrate on decreasing make span and budget; little concern has been paid to contemplate tasks and data sets dependency. In this paper, we introduced workflow scheduling technique to overcome data transfer and execute workflow tasks within deadline and budget constraints. The proposed techniques consist of initial data placement stage, which clusters and distributes datasets based on their dependence and replication-based partial critical path (R-PCP) technique which schedules tasks with data locality and dynamically maintains dependency matrix for the placement of generated data sets. To reduce run time datasets movement, we use interdata centre tasks replication and data sets replication to make sure data sets availability. Simulation results with four workflow applications illustrate that our strategy efficiently reduces data movement and executes all chosen workflows within user specified budget and deadline. Results reveal that R-PCP has 44.93% and 31.37% less data movement compared to random and adaptive data-aware scheduling (ADAS) techniques, respectively. R-PCP has 26.48% less energy consumption compared with ADAS technique.

On Scheduling Performance of Multi-User Full-Duplex Two-Way Relaying System With Rician Distributed RSI

In this paper, a multi-user full-duplex (FD) two-way relaying system with decode-and-forward protocol is considered where all the nodes are assumed to be mobile and to have FD abilities. The residual self-interference (RSI) at each node is modeled as a Rician distributed random variable and the effect of mobility is incorporated by adopting the first order auto-regressive (AR) model. Then, the signal-to-interference-plus-noise-ratio (SINR) based scheduling schemes namely random scheduling, absolute channel power-based (CPB) scheduling, hybrid scheduling, and normalized CPB scheduling, are modified and the user pair selection is carried out on the basis of instantaneous channel statistics. The performance of the considered framework is analyzed for the modified scheduling schemes in terms of error probability and average rate. Next, the closed-form expressions for the symbol error probability (SEP) and average rate are derived for independent and non-identically distributed Rayleigh fading channels. Also, the numerical analysis highlighting the impact of user mobility and imperfect channel estimation on the scheduling strategies, fairness is presented. Furthermore, the impacts of the degree of traffic asymmetry, scheduling fairness, user mobility, channel estimation errors and RSI on the system performance are investigated. Numerical results are validated through the Monte Carlo simulations.

UW-SEEDEX: A Pseudorandom-Based MAC Protocol for Underwater Acoustic Networks

Underwater wireless acoustic networks (UWANs) take advantage of acoustic communication to enable many distinct applications. The peculiar features of underwater acoustic channels, such as long propagation delay, high bit error rates, and severely limited bandwidth, make the use of medium access control (MAC) solutions designed for terrestrial radio networks inefficient in UWANs. This paper proposes UW-SEEDEX, a MAC protocol for UWANs that employs random time slot schedules, created from seeds, to avoid collisions. After exchanging seeds, nodes can know other’s entire schedules, allowing them to then better plan their transmissions. Simulations evaluate how each of UW-SEEDEX’s parameter affects its performance in metrics such as end-to-end delay, energy consumption, transmissions per data reception, and reception rate using different test scenarios. Simulations also show that UW-SEEDEX can perform better than other MAC solutions, delivering more messages than protocols such as UW-Aloha and Slotted FAMA and reduced, on average, up to three times the number of transmissions required for each message reception in networks with grid topologies. UW-SEEDEX presented reception rates close to 100 percent, low energy cost, and fewer transmissions per data reception. Our code is available at <uri xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">https://gitlab.com/epmcj/ns-3-dev/-/tree/new-uan-mac-protocols</uri> .

The clinical efficacy of external application of mirabilite and rhubarb combined with intrathoracic chemotherapy in treating malignant pleural effusion: A prospective, randomized, controlled clinical trial.

Background:Malignant pleural effusion (MPE) is one of the commonest causes of an exudative pleural effusion. Breathlessness, dyspnea and other symptoms often seriously distress and affect the quality of life. The external application of mirabilite and rhubarb (EAMR) combined with intrathoracic infusion of cisplatin, as an alternative treatment for MPE, is popular in China. The study aims to assess its effectiveness and safety combined with intrathoracic chemotherapy.Methods:This study is a prospective, randomized controlled clinical trial. Patient visits were performed at baseline and days 14 and 28 after treatment. Clinical outcomes were measured after chest drain placement using the criterion of efficacy refer to WHO standard, and QLQ-C30 questionnaire.Results:Database records of patients treated in our institution for MPE between October, 2016 and March, 2019. The study included 84 eligible patients. They were categorized with a randomization schedule into treatment group (N = 42) and control group (N = 42). There is statistical significance in the comparison of the total effective rate between these 2 groups (66.67% vs 54.76%, P < .05). Furthermore, there is statistical significance in the comparison of items of Physical (1.95 ± 0.50 vs 2.19 ± 0.58%, P < .05), Pain (1.98 ± 0.42 vs 2.07 ± 0.32, P < .05), and Global Health (1.23 ± 0.64 vs 1.13 ± 0.23%, P < .05) between these 2 groups. None of the patients had adverse reactions such as skin allergy and chest tightness.Conclusions:The total effective rate of treatment group using extra external application of mirabilite rhubarb powder is significantly higher than that of control group. The improvement of patients’ clinical symptoms is greater in treatment group and no adverse reactions is found. Therefore, external application of mirabilite and rhubarb combined with intrathoracic infusion of cisplatin is an effective method for the treatment of MPE, which is worth popularizing.

The effect of learner-adapted practice schedule and task similarity on motivation and motor learning in older adults

The purpose of the present study was to investigate the effect of learner-adapted practice schedule and task similarity on intrinsic motivation and motor learning in older adults. For this purpose, 60 right-handed older adults were randomly divided into six groups of blocked-similar, learner-adapted-similar, random-similar, blocked-dissimilar, learner-adapted-dissimilar, and random-dissimilar. Sequential timing was used as the task, and the intrinsic motivation questionnaire was used for measuring individuals' motivation. The learner-adapted practice was included performing the task in a combination of blocked, serial, and random orders according to error number in each block. The results showed that the learner-adapted practice significantly outperformed than other practice schedules in motivation and motor learning measures in similar and dissimilar conditions. Also, the random schedule resulted in superior performance than the blocked schedule in similar and dissimilar conditions. These findings were discussed according to the challenge point framework.

Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial

BackgroundTo date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19.MethodsIn this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ2 test following an intention-to-treat principle. Prespecified analysis of the primary endpoint, adjusted for baseline viral load, using bivariate logistic regression was done. The trial is now complete. This trial is registered with ClinicalTrials.gov, NCT04354259.FindingsBetween May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15–16·73; p=0·029). Of those with baseline viral load above 106 copies per mL, 15 (79%) of 19 patients in the peginterferon lambda group had undetectable virus on day 7, compared with six (38%) of 16 in the placebo group (OR 6·25 [95% CI 1·49–31·06]; p=0·012). Peginterferon lambda was well tolerated, and adverse events were similar between groups with mild and transient aminotransferase, concentration increases more frequently observed in the peginterferon lambda group. Two individuals met the threshold of grade 3 increase, one in each group, and no other grade 3 or 4 laboratory adverse events were reported.InterpretationPeginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding.FundingThe Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial

Voriconazole has been recommended as primary treatment for patients with invasive aspergillosis. Intravenous and tablet formulations of posaconazole that have improved systemic absorption could be an effective alternative to voriconazole. We aimed to assess non-inferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis. We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). Posaconazole was non-inferior to voriconazole for all-cause mortality up until day 42 in participants with invasive aspergillosis. Posaconazole was well tolerated, and participants had fewer treatment-related adverse events than in the voriconazole group. This study supports the use of posaconazole as a first-line treatment for the condition. Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.

Preliminary analysis of the antimicrobial activity of a novel surgical incise drape containing chlorhexidine gluconate against methicillin-resistant Staphylococcus aureus (MRSA) in an in vivo porcine, incisional-wound model

Surgical site infections occur in at least 2%-4% of all patients. A proposed, risk-reduction strategy has been the use of adhesive, plastic incise drapes to reduce the risk of surgical site infection. The present investigation reports the efficacy of a novel chlorhexidine gluconate (CHG) adhesive surgical drape to reduce the risk of horizontal bacterial migration into surgical wounds, using a porcine model of wound contamination. Using a standardized inoculum, and a predetermined randomization schedule, a porcine model was used to assess the efficacy of a CHG-impregnated adhesive drape to prevent MRSA contamination of a simulated surgical wound and intact skin surface compared with an iodophor-impregnated incise drape and a nonantimicrobial incise drape in 0, 1, and 4-hour surgeries. MRSA recovery from incisional wounds was lowest in sites treated with the CHG drape. The difference was statistically significant (P < .001) at all time points, both between the CHG drape and the nonantimicrobial control as well as between the CHG and iodophor drapes. Mean MRSA recovery from wounds treated with iodophor drapes was slightly lower than nonantimicrobial drapes. The difference was not statistically significant at 0- or 1-hour (P = .065 and P = .089, respectively), however the differences were significant at 4-hours (P = .024). These preliminary results show that a novel CHG surgical incise drape reduced MRSA contamination of a surgical incision site and showed significant antimicrobial activity against contamination of intact skin surfaces compared with an iodophor- impregnated drape. A novel CHG surgical drape was effective in significantly reducing MRSA contamination in an incisional wound model. Future studies are needed to assess its clinical efficacy.

A polymorphic heterogeneous security architecture for edge-enabled smart grids

The emergence of edge computing alleviates the network congestion, delay, and packet loss of cloud computing enabled smart grid architecture in big data scenarios, greatly improving the operation efficiency and communication quality of the smart grid. However, edge computing architecture also brings great security risks to the smart grid. This paper proposes a Polymorphic Heterogeneous Security Architecture (PHSA) for edge enabled smart grid, to assure the key services in the smart grid. Based on the dynamic heterogeneous redundancy architecture, the proposed architecture introduces intelligent scheduling of executors, intelligent arbitration of multi-state service response, cleaning and reconstruction of executors, and attack surface management. We establish a closed-loop core control process of decision and processing, adjustment and scheduling, cleaning reconstruction, migration, and recovery. Furthermore, a dynamic scheduling algorithm based on executor credit and heterogeneity is proposed. The simulation results show that, compared with the traditional smart grid security architecture, the PHSA has better defense ability and system reliability, significantly improving the security of edge enabled smart grid system. Besides, compared with the random scheduling strategy, the proposed dynamic executor scheduling algorithm can further improve the security of the system.

Model and algorithm for vessel scheduling optimisation through the compound channel with the consideration of tide height

To optimise vessel scheduling passing a compound channel with the water depth influenced by the periodic tide, this study establishes the vessel scheduling model through a typical tidal compound channel. In addition, based on the actual tidal data of the channel, a tide height computation function varying with time is obtained. Then a designed genetic algorithm (GA) is utilised to verify the model by the actual vessels' data through the Tianjin Port Fairway. The test experiment shows that the organisation efficiency is better than other methods, including larger draft vessels first (LDF), first come first served (FCFS), random scheduling (RS) and manual scheduling. It can take full advantage of the high tide and improve the vessel scheduling efficiency of a compound channel. With minor alterations, the proposed model and designed algorithm can also serve for vessel traffic organisation in other compound channels affected by tide water as well.

My Baby's Movements: A Stepped-Wedge Cluster-Randomised Controlled Trial of a Fetal Movement Awareness Intervention to Reduce Stillbirths

Background: Maternal perception of decreased fetal movements (DFM) is associated with stillbirth. The My Baby’s Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package for women and clinicians. Methods: A stepped wedge cluster randomised controlled trial was undertaken with 8 groups of 3-5 hospitals in Australia and New Zealand at four-monthly intervals, targeting women with a singleton pregnancy without major fetal anomaly at ≥28 weeks’ gestation. The primary outcome was stillbirth at ≥28 weeks’ gestation. Secondary outcomes included obstetric and neonatal outcomes. Analysis was undertaken using generalised linear mixed models controlling for calendar time, clustering, and hospital effects. Findings: From August 2016 to May 2019 there were 304,853 births with 290,219 meeting inclusion criteria: 150,079 in control and 140,140 in intervention periods. The stillbirth rate during the intervention was lower than the control period, although not statistically significant (2·2/1000 births versus 2·4, odds ratio [OR] 0·91, 95% Confidence Intervals [CI] 0·78-1·06, p=0·22). The decrease was larger across calendar time with 2·7/1000 in the first 18 months versus 2·0/1000 in the last 18 months (OR 0·74; 95% CI 0·63-0·86; p≤0·01). Adjusting for calendar time, stillbirth rates between the control and intervention periods were not significantly different: (aOR 1·18, 95% CI 0·93-1·50; p=0·18). No increase in obstetric intervention or adverse neonatal outcome was evident. Interpretation: The MBM intervention did not reduce stillbirths beyond the downward trend over time, suggesting hospitals may have implemented best practice in DFM management outside their randomisation schedule. Based on these findings, the role of interventions for raising awareness of DFM remains unclear. Trial Registration: ACTRN12614000291684. Funding Statement: National Health and Medical Research Council (NHMRC) Project Grant Application (APP1067363). Stillbirth Foundation Australia provided funding to develop the MBM application. Dr Glenn Gardener was provided a Betty McGrath Fellowship through the Mater Research Institute. Additional support was provided by Mater Foundation and the NHMRC Stillbirth Centre of Research Excellence. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Primary ethics approval was obtained from Mater Misericordiae Ltd Human Research Ethics Committee (EC00332) (MML HREC) in 2015. Further jurisdictional ethics approval was obtained from seven participating HRECs include the ACT Health, Northern Sydney Local Health District (NSLHD), Northern Territory Department of Health and Menzies School of Health Research, The Central Health and Disability Ethics Committee (NZ), Melbourne Health, and the Mercy Health. Governance clearance was obtained from all 26 sites involved in the trial.

Research on Equipment Configuration Optimization of AGV Unmanned Warehouse

To improve the throughput performance of the autonomous guide vehicle (AGV) unmanned storage system, a two-stage mathematical model was established. The model also considers the equipment configuration of the AGV unmanned storage system and the AGV- picking stations dual resource coordination scheduling problem. In the equipment-task scheduling phase, the model aims at the shortest order completion time, while the equipment configuration and layout model aims at the minimum equipment configuration and operating cost. To solve the two-stage model, a two-layer genetic algorithm was designed. The inner layer algorithm was used to optimize the task scheduling order of AGVs and picking stations. The results of the inner layer algorithm are fed back to the outer model to optimize configuration of the equipment and the picking station's layout. The inner and outer loops are combined to obtain the optimal equipment configuration scheme. Through the simulation study of an enterprise AGV unmanned storage case, the optimal equipment configuration combination and picking stations layout scheme are obtained. Compared with the equipment configuration scheme based on the principle the task scheduling in operation is another key link that affects the picking efficiency of an unmanned warehouse of random task scheduling and the principle of shortest job time first; The model can improve the efficiency of warehouse retrieval and minimize the number of equipment configurations. Finally, the improved genetic algorithm is used to solve the model, and the performance is compared with that of LINGO to verify the effectiveness of the improved algorithm.

Power-to-gas-based VPP Stochastic Scheduling Optimization Model in View of Carbon Emission Constraints

Combining P2G and virtual power plant (Virtual power plant, VPP), this paper proposes a new concept of electrical interconnection virtual power plant (Power-to-gas-based VPP, GVPP). In addition, this paper proposes a GVPP low-carbon economic dispatch optimization model considering carbon emission rights trading. Furthermore, in view of the strong uncertainty of wind power and PV power generation in GVPP, the information gap decision theory is used to measure the uncertainty tolerance threshold of decision makers under different expected target deviations. In addition, a GVPP near-zero carbon random scheduling optimization model is established under the conventional and worst-case scenarios. In order to verify the feasibility and effectiveness of the proposed model, a 9-node energy hub was selected as the simulation system. The results show that: (1) GVPP can coordinate and optimize the output of electricity-to-gas and gas turbines according to the difference in gas and electricity prices in the electricity market and the natural gas market at different times. Moreover, it can use the two-way conversion of gas and electricity energy to form an electricity-gas-electricity cycle, thereby improving the system’s clean energy absorption capacity, reducing its own carbon emissions and the volatility of net output. (2) The IGDT method can be used to describe the impact of wind and wind uncertainty in GVPP. Decision makers can obtain the maximum tolerance for wind and wind uncertainty by setting a reasonable expected target deviation coefficient. For example, when the expected target deviation coefficient is 0.5, the corresponding degree of uncertainty is 0.142. In the worst scenario, the scheduling results obtained by this method are in line with the actual scheduling experience, which reflects the effectiveness of the method in this paper. In summary, the models and methods presented in this paper can be used to formulate optimal scheduling decision-making schemes for GVPP considering carbon trading and uncertainty.

Safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of the oral TYK2 inhibitor PF-06826647 in participants with plaque psoriasis: a phase 1, randomised, double-blind, placebo-controlled, parallel-group study

Summary Background Blockade of tyrosine kinase 2 (TYK2) signalling has previously shown therapeutic potential in the treatment of psoriasis. The primary objective of this study was to assess the safety and tolerability of the TYK2 inhibitor PF-06826647. Methods This phase 1, randomised, double-blind, placebo-controlled, parallel-group study assessed once daily oral dosing of PF-06826647 in participants with plaque psoriasis, at a single clinical research site in the USA. Eligible participants (aged 18–65 years) had plaque psoriasis covering at least 15% of total body surface area and a psoriasis area and severity index (PASI) score of at least 12 at baseline. Participants received PF-06826647 (100 mg or 400 mg), or placebo once daily for 28 days. Using a computer-generated randomisation schedule with a block size of 3, participants were sequentially randomly assigned into two cohorts by the investigator; in the first cohort, participants were randomly assigned in a 2:1 ratio to receive either oral PF-06826647 400 mg or placebo once daily, whereas participants in the second cohort were randomly assigned in a 2:1 ratio to receive either oral PF-06826647 100 mg or placebo once daily. Site, investigator, Pfizer personnel, and participants, were masked to treatment. The primary endpoint was the safety of multiple-dose PF-06826647 in participants with plaque psoriasis. Secondary endpoints were the characterisation of the pharmacokinetics of multiple-dose PF-06826647 in plasma and the change in PASI score at day 28. Safety analysis was done in all participants who received at least one dose of study drug. Efficacy analysis was done in all participants who received at least one dose of randomised study drug, and had a baseline and at least one post-baseline measurement. This study is registered as a randomised, controlled trial with ClinicalTrials.gov , NCT03210961 and is completed. Findings The trial was done between July 14, 2017, and Jan 25, 2019. Overall from 91 participants assessed, 40 participants with moderate-to-severe psoriasis were randomly assigned to treatment (placebo 14 [35%] of 40; PF-06826647 100 mg, 11 [28%] of 40; PF-06826647 400 mg, 15 [38%] of 40). Treatment-emergent adverse events (TEAEs) were reported in 12 (80%) of 15 participants in the PF-06826647 400 mg group, seven (50%) of 14 in the placebo group and five (45%) of 11 in the 100 mg group. All TEAEs were mild in severity, except one moderate TEAE of vomiting reported in the placebo group. There were no deaths, serious TEAEs, severe TEAEs, dose reductions, or temporary discontinuations. Compared with placebo, the change from baseline in PASI score at day 28 showed a significant reduction in least squares mean difference for the PF-06826647 400 mg group (−13·05; 90% CI −18·76 to −7·35; p=0·00077) but not for the PF-06826647 100 mg group (−3·49; −9·48 to 2·50; p=0·33). Both the area under the concentration–time curve over the dosing interval and the maximum concentration increased in a less than dose proportional manner with increasing dose from 100 mg to 400 mg PF-06826647. Interpretation PF-06826647 showed significant improvement in disease activity within 4 weeks of dosing with an acceptable safety profile. PF-06826647 holds promise over conventional oral treatments for psoriasis that have shown limited efficacy or unfavourable safety profiles. Funding Pfizer.

The Role of Haptic Expectations in Reaching to Grasp: From Pantomime to Natural Grasps and Back Again

When we reach to pick up an object, our actions are effortlessly informed by the object’s spatial information, the position of our limbs, stored knowledge of the object’s material properties, and what we want to do with the object. A substantial body of evidence suggests that grasps are under the control of “automatic, unconscious” sensorimotor modules housed in the “dorsal stream” of the posterior parietal cortex. Visual online feedback has a strong effect on the hand’s in-flight grasp aperture. Previous work of ours exploited this effect to show that grasps are refractory to cued expectations for visual feedback. Nonetheless, when we reach out to pretend to grasp an object (pantomime grasp), our actions are performed with greater cognitive effort and they engage structures outside of the dorsal stream, including the ventral stream. Here we ask whether our previous finding would extend to cued expectations for haptic feedback. Our method involved a mirror apparatus that allowed participants to see a “virtual” target cylinder as a reflection in the mirror at the start of all trials. On “haptic feedback” trials, participants reached behind the mirror to grasp a size-matched cylinder, spatially coincident with the virtual one. On “no-haptic feedback” trials, participants reached behind the mirror and grasped into “thin air” because no cylinder was present. To manipulate haptic expectation, we organized the haptic conditions into blocked, alternating, and randomized schedules with and without verbal cues about the availability of haptic feedback. Replicating earlier work, we found the strongest haptic effects with the blocked schedules and the weakest effects in the randomized uncued schedule. Crucially, the haptic effects in the cued randomized schedule was intermediate. An analysis of the influence of the upcoming and immediately preceding haptic feedback condition in the cued and uncued random schedules showed that cuing the upcoming haptic condition shifted the haptic influence on grip aperture from the immediately preceding trial to the upcoming trial. These findings indicate that, unlike cues to the availability of visual feedback, participants take advantage of cues to the availability of haptic feedback, flexibly engaging pantomime, and natural modes of grasping to optimize the movement.

How much HVAC energy could be saved from the occupant-centric smart home thermostat: A nationwide simulation study

Thermostat management plays a significant role in household energy conservation. This study aims to conduct a systematic and comprehensive analysis to quantify the energy savings potential of the occupant-centric smart thermostat based on a large-scale nationwide simulation infrastructure. The single-family Residential Prototype Building Model was used to represent a typical single-family detached house in the U.S. A generalized random occupancy presence schedule was created based on an occupancy probability schedule and k-means clustering algorithm. A total of 16,000 simulations, which were composed of four building foundation types, four heating source types, 40 American cities, five building energy code versions, and five thermostat control strategies, were conducted to evaluate the performances of the smart home thermostat in terms of saving building energy usage and maintaining occupant thermal comfort. The nationwide simulation results suggested that the temperature setback control during the unoccupied period could achieve some energy savings in the U.S. households. However, only very few of the 40 cities could see an annual Heating, Ventilation, and Air-conditioning energy savings ratio of over 30%. Besides, the implementation of the occupied standby temperature reset could greatly increase the peak load of the HVAC system and contribute to the grid load imbalance issue. It’s also worth noting that the smart recovery feature is proved to be able to bring additional benefits for a smart home thermostat. It could decrease the temperature setpoint not met time by about 30 min, and relieve the thermal discomfort due to the temperature setback control.

Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study

Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing. Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1. ViiV Healthcare and Janssen.

Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial

Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18-75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36-73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6-30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3-67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7-59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. National Heart, Lung, and Blood Institute.

Dissimilar Phonemes Create a Contextual Interference Effect During a Nonword Repetition Task.

Purpose: The contextual interference effect is a motor learning phenomenon where conditions that decrease overall learning during practice enhance overall learning with new tasks. In the limb literature, this effect is observed when different practice conditions are used (e.g., blocked vs. random practice schedules). In speech motor learning, contextual interference effects are mixed. The differences observed during speech motor learning may be due to the stimuli used. We hypothesized that dissimilar phonemes might create interference during speech motor learning, such that training accuracy would decrease. However, generalization accuracy would increase compared to practice with nonwords containing similar phonemes. Method: Thirty young adults with typical speech and hearing participated in a motor learning study using a cross-over design. Participants engaged in nonword repetition training followed by an immediate retention and transfer task with two sets of nonwords: nonwords with similar phonemes and nonwords with dissimilar phonemes. Percent consonants correct were calculated to examine the effects of the two different types of nonwords based on the stage of skill acquisition. Results: A contextual interference effect was observed in this study using nonwords that varied in phonemic similarity. Nonwords with similar phonemes were produced with greater accuracy during the training stage of skill acquisition, and nonwords with dissimilar phonemes were produced with greater accuracy during the transfer stage. Conclusion: The proposed hypothesis for this study was met – practicing nonwords with dissimilar phonemes resulted in greater accuracy in the transfer phase of this experiment. Results indicate that phonemic dissimilarity produced contextual interference and influenced speech motor learning. These results indicate that the linguistic properties of stimuli must be factored into speech motor learning. Future research should explore if other linguistic variables interact with variables of motor learning to enhance speech practice and generalization outcomes.