bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical methods for non-adherence in non-inferiority trials: useful and used? A systematic review
Authors: Dodd Matthew , Fielding Katherine , Carpenter James R , Thompson Jennifer A , Elbourne Diana
Published: January 2022

Background

In non-inferiority trials with non-adherence to interventions (or non-compliance), intention-to-treat and per-protocol analyses are often performed; however, non-random non-adherence generally biases these estimates of efficacy.

Objective

To identify statistical methods that adjust for the impact of non-adherence and thus estimate the causal effects of experimental interventions in non-inferiority trials.

Design

A systematic review was conducted by searching the Ovid MEDLINE database (31 December 2020) to identify (1) randomised trials with a primary analysis for non-inferiority that applied (or planned to apply) statistical methods to account for the impact of non-adherence to interventions, and (2) methodology papers that described such statistical methods and included a non-inferiority trial application.

Outcomes

The statistical methods identified, their impacts on non-inferiority conclusions, and their advantages/disadvantages.

Results

A total of 24 papers were included (4 protocols, 13 results papers and 7 methodology papers) reporting relevant methods on 26 occasions. The most common were instrumental variable approaches (n=9), including observed adherence as a covariate within a regression model (n=3), and modelling adherence as a time-varying covariate in a time-to-event analysis (n=3). Other methods included rank preserving structural failure time models and inverse-probability-of-treatment weighting. The methods identified in protocols and results papers were more commonly specified as sensitivity analyses (n=13) than primary analyses (n=3). Twelve results papers included an alternative analysis of the same outcome; conclusions regarding non-inferiority were in agreement on six occasions and could not be compared on six occasions (different measures of effect or results not provided in full).

Conclusions

Available statistical methods which attempt to account for the impact of non-adherence to interventions were used infrequently. Therefore, firm inferences about their influence on non-inferiority conclusions could not be drawn. Since intention-to-treat and per-protocol analyses do not guarantee unbiased conclusions regarding non-inferiority, the methods identified should be considered for use in sensitivity analyses.

PROSPERO registration number

CRD42020177458.
Study protocol for a prospective cohort study identifying risk factors for sport injury in adolescent female football players: the Karolinska football Injury Cohort (KIC)
Authors: Tranaeus Ulrika , Weiss Nathan , Lyberg Victor , Hagglund Martin , Waldén Markus , Johnson Urban , Asker Martin , Skillgate Eva
Published: January 2022

Introduction

Football is a popular sport among young females worldwide, but studies concerning injuries in female players are scarce compared with male players. The aim of this study is to identify risk factors for injury in adolescent female football players.

Methods and analysis

The Karolinska football Injury Cohort (KIC) is an ongoing longitudinal study that will include approximately 400 female football academy players 12–19 years old in Sweden. A detailed questionnaire regarding demographics, health status, lifestyle, stress, socioeconomic factors, psychosocial factors and various football-related factors are completed at baseline and after 1 year. Clinical tests measuring strength, mobility, neuromuscular control of the lower extremity, trunk and neck are carried out at baseline. Players are followed prospectively with weekly emails regarding exposure to football and other physical activity, health issues (such as stress, recovery, etc), pain, performance and injuries via the Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC-O). Players who report a substantial injury in the OSTRC-O, that is, not being able to participate in football activities, or have reduced their training volume performance to a moderate or major degree, are contacted for full injury documentation. In addition to player data, academy coaches also complete a baseline questionnaire regarding coach experience and education.

Ethics and dissemination

The study was approved by the Regional Ethical Review Authority at Karolinska Institutet, Stockholm, Sweden (2016/1251-31/4). All participating players and their legal guardians give their written informed consent. The study will be reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology. The results will be published in peer-reviewed academic journals and disseminated to the Swedish football movement through stakeholders and media.
Efficacy and cost-effectiveness of an online mindfulness program (MindOnLine) to reduce fear of recurrence among people with cancer: study protocol for a randomised controlled trial
Authors: Livingston Patricia M , Russell Lahiru , Orellana Liliana , Winter Natalie , Jefford Michael , Girgis Afaf , Austin David , O Eric , Mihalopoulos Cathrine , Ugalde Anna , Chambers Richard , Phipps-Nelson Jo , Herath Dishan , Botti Mari , Rasmussen Bodil , Whitfield Kathryn , Ftanou Maria , Smith Allan Ben , Pilatti Kirsten , Sara Sally , Wootten Addie , Gillan Kate , Singh Madhu , Campbell David , Pillay Brindha , White Victoria
Published: January 2022

Introduction

Fear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people’s well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer. A formal economic programme will also be conducted.

Methods and analysis

A single-blind randomised controlled trial to determine the efficacy and cost-efficacy of a MindOnLine programme for cancer survivors. A total of 400 people living with cancer will be recruited via online advertisements on social media platforms, peak consumer advocacy groups or through outpatient services at healthcare providers across Victoria, Australia. People will be randomly allocated to either the MindOnLine programme (n=200) or waitlist control (n=200). Participant assessments will occur at baseline, at 9 weeks and 9-month follow-up. The primary outcome is change in Fear of Recurrence Index Score total score between baseline and 9 weeks; secondary outcomes are changes in depression and anxiety, quality of life and mindfulness. The economic analysis comprises a cost-consequences analysis where all outcomes will be compared with costs.

Ethics and dissemination

Ethics approval was obtained from the Peter MacCallum Cancer Centre (20-53) and Deakin University (2020-284). All participants will be required to provide written informed consent. Findings will be disseminated in peer reviewed journals and among key stakeholder organisations including hospitals, cancer and community organisations and Government. If successful the project will be rolled out nationally with a formal implementation plan.

Trial registration number

Australian New Zealand Clinical Trials Registry (12620000645954); Pre-results. Registered 6 June 2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379520&isReview=true.
Factors associated with the risk of HIV infection among HIV-exposed infants in Malawi: 2013–2020
Authors: Ng'ambi Wingston Felix , Merzouki Fatma Aziza , Estill Janne , Orel Erol , Chimpandule Tiwonge , Nyirenda Rose , Keiser Olivia
Published: January 2022

Background

Despite the availability of individual-level data of infants accessing HIV DNA-PCR testing service, there has been little in-depth analysis of such data. Therefore, we describe trends in risk of HIV infection among Malawi’s HIV-exposed infants (HEI) with DNA-PCR HIV test result from 2013 to 2020.

Methods

This is an implementation study using routinely collected patient-level HIV DNA-PCR test result data extracted from the national Laboratory Management Information System database managed by the Department of HIV/AIDS between 1 January 2013 and 30 June 2020. We calculated frequencies, proportions and odds ratio (OR) with their associated 95% CI. We performed a random-effects logistic regression to determine the risk factors associated with HIV infection in infants, controlling for the spatial autocorrelation between districts and adjusting for other variables.

Results

We evaluated 255 229 HEI across 750 facilities in 28 districts. The HIV DNA-PCR test was performed within 2 months in 57% of the children. The overall HIV prevalence among all tested HEI between 2013 and 2020 was 7.2% (95% CI 7.1% to 7.3%). We observed a decreasing trend in the proportion of HEI that tested HIV positive from 7.0% (95% CI 6.6% to 7.4%) in 2013 to 5.7% (95% CI 5.4% to 5.9%) in 2015 followed by an increase to 9.9% (95% CI 9.6% to 10.2%) in 2017 and thereafter a decreasing trend between 2017 (i.e. 9.72% (95%CI: 9.43-10.01)) and 2020 (i.e. 3.86% (95%CI: 3.34-4.37)). The HIV prevalence increased by age of the HEI. There was spatial heterogeneity of HIV prevalence between districts of Malawi. The prevalence of HIV was higher among the HEI from the Northern region of Malawi.

Conclusion

The main findings of the study are that the DNA test is performed within 2 months only in 57% of the children, that the decreasing trend of HIV prevalence among HEI observed up to 2015 was followed by an increase up to 2017 and a decrease afterwards, and that the risk of HIV infection increased with age at HIV testing. We summarised spatial and temporal trends of risk of HIV infection among HEI in Malawi between 2013 and 2020. There is need to ensure that all the HEI are enrolled in HIV care by 8 weeks of age in order to further reduce the risk of HIV in this population.
Fast-track hospital end-of-life discharge pathway: is it actually fast? National clinical audit
Authors:   Geriatric Medicine Research Collaborative
Published: January 2022

Objectives

To determine adherence to Department of Health and Social Care target of fast-track pathway discharge for end-of-life care within 48 hours.

Methods

Multicentre audit in England using retrospective analysis of patient records for fast-track pathway tools submitted between 1 March 2019 and 31 March 2019.

Results

Most patients (72%) were not discharged within the 48-hour target. There was significant variability in success between hospital sites. Delays in discharge were most frequently considered to be secondary to delays in sourcing packages of care and 24-hour care facility placements. Involvement of specialist discharge nurses in paperwork submission improved rates by Commissioning Care Groups. Patients who died in hospital had significantly longer admissions than those who were discharged (discharged 19 days (IQR 11–28) vs died 28 days (IQR 18–42); p=0.039). This was entirely accounted for by increased numbers of days between admission and first suggestion of fast-track pathway discharge in those who died in hospital (discharged 9 days (IQR 5–19), died 15 days (IQR 9–33); p=0.003).

Conclusions

We demonstrated a delay in the fast-track pathway discharge process with significant variation in success of the discharge process at different geographical locations.
Cardiovascular computed tomography imaging for coronary artery disease risk: plaque, flow and fat
Authors: Channon Keith M , Newby David E , Nicol Edward D , Deanfield John
Published: January 2022

Cardiac imaging is central to the diagnosis and risk stratification of coronary artery disease, beyond symptoms and clinical risk factors, by providing objective evidence of myocardial ischaemia and characterisation of coronary artery plaque. CT coronary angiography can detect coronary plaque with high resolution, estimate the degree of functional stenosis and characterise plaque features. However, coronary artery disease risk is also driven by biological processes, such as inflammation, that are not fully reflected by severity of stenosis, myocardial ischaemia or by coronary plaque features. New cardiac CT techniques can assess coronary artery inflammation by imaging perivascular fat, and this may represent an important step forward in identifying the ‘residual risk’ that is not detected by plaque or ischaemia imaging. Coronary artery disease risk assessment that incorporates clinical factors, plaque characteristics and perivascular inflammation offers a more comprehensive individualised approach to quantify and stratify coronary artery disease risk, with potential healthcare benefits for prevention, diagnosis and treatment recommendations. Furthermore, identifying new biomarkers of cardiovascular risk has the potential to refine early-life prevention strategies, before atherosclerosis becomes established.
Interrupting the nitrosative stress fuels tumor-specific cytotoxic T lymphocytes in pancreatic cancer
Authors: De Sanctis Francesco , Lamolinara Alessia , Boschi Federico , Musiu Chiara , Caligola Simone , Trovato Rosalinda , Fiore Alessandra , Frusteri Cristina , Anselmi Cristina , Poffe Ornella , Cestari Tiziana , Canè Stefania , Sartoris Silvia , Giugno Rosalba , Del Rosario Giulia , Zappacosta Barbara , Del Pizzo Francesco , Fassan Matteo , Dugnani Erica , Piemonti Lorenzo , Bottani Emanuela , Decimo Ilaria , Paiella Salvatore , Salvia Roberto , Lawlor Rita Teresa , Corbo Vincenzo , Park Youngkyu , Tuveson David A , Bassi Claudio , Scarpa Aldo , Iezzi Manuela , Ugel Stefano , Bronte Vincenzo
Published: January 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors owing to its robust desmoplasia, low immunogenicity, and recruitment of cancer-conditioned, immunoregulatory myeloid cells. These features strongly limit the success of immunotherapy as a single agent, thereby suggesting the need for the development of a multitargeted approach. The goal is to foster T lymphocyte infiltration within the tumor landscape and neutralize cancer-triggered immune suppression, to enhance the therapeutic effectiveness of immune-based treatments, such as anticancer adoptive cell therapy (ACT).

Methods

We examined the contribution of immunosuppressive myeloid cells expressing arginase 1 and nitric oxide synthase 2 in building up a reactive nitrogen species (RNS)-dependent chemical barrier and shaping the PDAC immune landscape. We examined the impact of pharmacological RNS interference on overcoming the recruitment and immunosuppressive activity of tumor-expanded myeloid cells, which render pancreatic cancers resistant to immunotherapy.

Results

PDAC progression is marked by a stepwise infiltration of myeloid cells, which enforces a highly immunosuppressive microenvironment through the uncontrolled metabolism of L-arginine by arginase 1 and inducible nitric oxide synthase activity, resulting in the production of large amounts of reactive oxygen and nitrogen species. The extensive accumulation of myeloid suppressing cells and nitrated tyrosines (nitrotyrosine, N-Ty) establishes an RNS-dependent chemical barrier that impairs tumor infiltration by T lymphocytes and restricts the efficacy of adoptive immunotherapy. A pharmacological treatment with AT38 ([3-(aminocarbonyl)furoxan-4-yl]methyl salicylate) reprograms the tumor microenvironment from protumoral to antitumoral, which supports T lymphocyte entrance within the tumor core and aids the efficacy of ACT with telomerase-specific cytotoxic T lymphocytes.

Conclusions

Tumor microenvironment reprogramming by ablating aberrant RNS production bypasses the current limits of immunotherapy in PDAC by overcoming immune resistance.
Cost-effectiveness of thrombectomy in patients with minor stroke and large vessel occlusion: effect of thrombus location on cost-effectiveness and outcomes
Authors: Khunte Mihir , Wu Xiao , Koo Andrew , Payabvash Seyedmehdi , Matouk Charles , Heit Jeremy J , Wintermark Max , Albers Gregory W , Sanelli Pina C , Gandhi Dheeraj , Malhotra Ajay
Published: January 2022

Background

To evaluate the cost-effectiveness of endovascular thrombectomy (EVT) to treat large vessel occlusion (LVO) in patients with acute, minor stroke (National Institute of Health Stroke Scale (NIHSS) <6) and impact of occlusion site.

Methods

A Markov decision-analytic model was constructed accounting for both costs and outcomes from a societal perspective. Two different management strategies were evaluated: EVT and medical management. Base case analysis was done for three different sites of occlusion: proximal M1, distal M1 and M2 occlusions. One-way, two-way and probabilistic sensitivity analyses were performed.

Results

Base-case calculation showed EVT to be the dominant strategy in 65-year-old patients with proximal M1 occlusion and NIHSS <6, with lower cost (US$37 229 per patient) and higher effectiveness (1.47 quality-adjusted life years (QALYs)), equivalent to 537 days in perfect health or 603 days in modified Rankin score (mRS) 0–2 health state. EVT is the cost-effective strategy in 92.7% of iterations for patients with proximal M1 occlusion using a willingness-to-pay threshold of US$100 000/QALY. EVT was cost-effective if it had better outcomes in 2%–3% more patients than intravenous thrombolysis (IVT) in absolute numbers (base case difference −16%). EVT was cost-effective when the proportion of M2 occlusions was less than 37.1%.

Conclusions

EVT is cost-effective in patients with minor stroke and LVO in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with non-reperfusion. Our study emphasizes the need for caution in interpreting previous observational studies which concluded similar results in EVT versus medical management in patients with minor stroke due to a high proportion of patients with M2 occlusions in the two strategies.
Successful mechanical thrombectomy in acute ischemic stroke: revascularization grade and functional independence
Authors: Ghozy Sherief , Kacimi Salah Eddine Oussama , Azzam Ahmed Y , Farahat Ramadan Abdelmoez , Abdelaal Abdelaziz , Kallmes Kevin M , Adusumilli Gautam , Heit Jeremy J , Kadirvel Ramanathan , Kallmes David F
Published: January 2022

Most studies define the technical success of endovascular thrombectomy (EVT) as a Thrombolysis in Cerebral Infarction (TICI) revascularization grade of 2b or higher. However, growing evidence suggests that TICI 3 is the best angiographic predictor of improved functional outcomes. To assess the association between successful TICI revascularization grades and functional independence at 90 days, we performed a systematic review and network meta-analysis of thrombectomy studies that reported TICI scores and functional outcomes, measured by the modified Rankin Scale, using the semi-automated AutoLit software platform. Forty studies with 8691 patients were included in the quantitative synthesis. Across TICI, modified TICI (mTICI), and expanded TICI (eTICI), the highest rate of good functional outcomes was observed in patients with TICI 3 recanalization, followed by those with TICI 2c and TICI 2b recanalization, respectively. Rates of good functional outcomes were similar among patients with either TICI 2c or TICI 3 grades. On further sensitivity analysis of the eTICI scale, the rates of good functional outcomes were equivalent between eTICI 2b50 and eTICI 2b67 (OR 0.81, 95% CI 0.52 to 1.25). We conclude that near complete or complete revascularization (TICI 2c/3) is associated with higher rates of functional outcomes after EVT.
Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients
Authors: You Shoujiang , Han Qiao , Dong Xiaofeng , Zhong Chongke , Du Huaping , Sun Yaming , Cao Yongjun , Liu Chunfeng
Published: January 2022

Background

We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients.

Methods

A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92–0.98), Q3 (0.98–1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4–5) separately on discharge in AIS patients.

Results

Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge.

Conclusions

High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.
Tobacco tax evasion in Western Balkan countries: tax evasion prevalence and evasion determinants
Authors: Vladisavljevic Marko , Zubović Jovan , Jovanovic Olivera , Djukic Mihajlo , Trajkova Najdovska Natasa , Pula Ereza , Gligorić Dragan , Gjika Aida
Published: January 2022

Background and objective

Tobacco tax evasion undermines the goal of tobacco taxes as a tobacco control measure to make tobacco products less affordable, increases the health risks for those who smoke and decreases the government revenue. This paper analyses the tobacco tax evasion in six Western Balkan (WB) countries: Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia. The aim of this research is to estimate the size of the illicit market and identify the main determinants of tax evasion activities in the Southeastern European region.

Data and methods

Data from 2019 Survey on Tobacco Consumption in Southeastern Europe (STC-SEE) are used. STC-SEE provides uniquely comparable nationally representative data on smoking behaviour for adult (18–85 years old) population for each country. Tax evasion is defined on the basis of available information on tax stamps, health warnings, price and the place of purchase, in accordance with the previous research on tax evasion. In order to estimate the determinants of illicit purchases we use binary choice model of tax evasion.

Results

The study finds that 20.4% of all current smokers in WB countries evade taxes on tobacco products, with evasion being much more frequent for hand-rolled (HR) tobacco (86.7%) than for the manufactured cigarettes (MC) (8.6%). While HR is predominantly illicit in all six countries, MC evasion varies significantly, with evasion being significantly higher in Montenegro and Bosnia and Herzegovina. Results further suggest that tax evasion is higher in the statistical regions where institutional capacities to tackle illicit trade are lower, in municipalities bordering countries with high MC evasion, as well as among smokers with low income, women and elderly. We also provide evidence that higher tobacco taxes and prices do not increase illicit consumption.

Conclusion

The findings from the research suggest that in order to decrease tax evasion, governments should put additional effort to strengthen institutional capacities to tackle illicit tobacco markets. Furthermore, improving regional coordination in development and implementation of tobacco control policies, including the prevention of illicit market, is essential in lowering evasion in all WB countries. Finally, WB countries should regulate and enforce excise tax stamp requirements on the HR tobacco market to a much higher degree.
Field performance of four vibrating-wire piezometer installation methods
Authors: Young Nathan , Lemieux Jean-Michel , Mony Laura , Germain Alexandra , Locat Pascal , Demers Denis , Locat Ariane , Locat Jacques
Published: January 2022

Vibrating-wire piezometers provide a number of advantages over the traditional hydraulic piezometer design. There are currently many methods and configurations for installing vibrating-wire piezometers, the most common being: single piezometers in sand packs (SP), multilevel piezometers in sand packs (MLSP), and fully grouted multilevel piezometers using either bentonite (FGB) or cement−bentonite grout (FGCB). This study assesses the performance of these four different installation methods at a field site possessing complex stratigraphy, including glacial and marine sediments. To accomplish this objective, pore pressure data recorded between December 2017 and July 2019 were analyzed. Data indicate that SP, MLSP, and FGB piezometers performed most reliably, because piezometers installed at the same depth with these methods recorded similar pressure variations that were coherent with the hydrogeological setting. Of the two fully grouted installations using cement−bentonite grout, one installation failed completely due to a hydraulic short circuit, likely caused by preferential flow occurring along the wires of the embedded instruments. The lack of a standard method for mixing cement−bentonite grout at the time of construction likely contributed to the failure of the FGCB installations, as the grout mixture used in this study was likely too viscous to provide a suitable seal.
Closing the window on WIMP Dark Matter
Authors: Bottaro Salvatore , Buttazzo Dario , Costa Marco , Franceschini Roberto , Panci Paolo , Redigolo Diego , Vittorio Ludovico
Published: January 2022

We study scenarios where Dark Matter is a weakly interacting particle (WIMP) embedded in an ElectroWeak multiplet. In particular, we consider real SU(2) representations with zero hypercharge, that automatically avoid direct detection constraints from tree-level Z-exchange. We compute for the first time all the calculable thermal masses for scalar and fermionic WIMPs, including Sommerfeld enhancement and bound states formation at leading order in gauge boson exchange and emission. WIMP masses of few hundred TeV are shown to be compatible both with s-wave unitarity of the annihilation cross-section, and perturbativity. We also provide theory uncertainties on the masses for all multiplets, which are shown to be significant for large SU(2) multiplets. We then outline a strategy to probe these scenarios at future experiments. Electroweak 3-plets and 5-plets have masses up to about 16 TeV and can efficiently be probed at a high energy muon collider. We study various experimental signatures, such as single and double gauge boson emission with missing energy, and disappearing tracks, and determine the collider energy and luminosity required to probe the thermal Dark Matter masses. Larger multiplets are out of reach of any realistic future collider, but can be tested in future $$\gamma $$
γ
-ray telescopes and possibly in large-exposure liquid Xenon experiments.
Influence of grooved volute casing parameters on pressure pulsation and erosion wear characteristics in a centrifugal pump
Authors: Shen Zhengjing , Han Wei , Zhong Yiming , Luo Bo , Li Rennian , Chu Wuli
Published: January 2022

Previous work has shown that performance and internal flow characteristics of a centrifugal pump can be significantly improved with grooved volute casing (GVC). However, it has been found that the selection of the design parameters of the groove structure also has a direct impact on the performance output, internal flow pressure pulsation and erosion wear characteristics of the overflow components of centrifugal pump, so it is necessary to further analyze the design rules of the groove structure parameters. In this study, we first investigated the influence of the number of grooves on the head, efficiency and unsteady pressure pulsation characteristics of the internal flow field of the centrifugal pump, and on this basis, the correlation between different particle parameters and the erosion wear of key overflow components under the conditions of solid–liquid two-phase flow were also studied, and the erosion wear characteristics of the inner wall of the volute casing of centrifugal pump with GVC and original volute casing (OVC) structures were compared. This research leads to the conclusion that when the number of grooves is 3, the groove structure has the least influence on the performance of the centrifugal pump, and the overall change of the performance curve is more stable. Additionally, the pressure pulsation at each monitoring point of the GVC under the same flow condition is smaller, and when the number of grooves increases, the pressure pulsation amplitude also decreases. When the number of grooves is 3, the GVC shows a more significant flow improvement effect under all flow conditions. Based on the improvement of the groove structure on the flow stability, the particle motion behavior can be affected at the same time, so that the pump with GVC can mitigate the erosion wear of the inner wall of the volute casing under the solid–liquid two-phase flow conditions, which improves the critical performance and service life of the key overflow components of the pump.
The rotation scheme of quantum states based on EPR pairs
Authors: Xiong Si-Yu , Tang Liang , Zhang Qun , Xue Dan , Bai Ming-Qiang , Mo Zhi-Wen
Published: January 2022

In this paper, we give a further discussion of short-distance teleportation. We propose bidirectional, rotation and cyclic rotation teleportation schemes for short-distance participants, respectively. In our bidirectional transmission scheme, the quantum channel is still an EPR pair and an auxiliary qubit in the ground state [Formula: see text], and two participants can transmit an unknown single-qubit state to each other. In the rotation and cyclic rotation schemes, bidirectional transmission is performed between two adjacent participants in turn. The unknown state qubits of the participants collapse into the ground state after one bidirectional transmission, and can be used as auxiliary qubits in subsequent bidirectional transmission. After a complete state rotation, each participant has held the unknown state of the other participants, and the last one owned by the participant is still the original unknown state. Although the schemes we proposed are applicable to a small range of transmission, they have certain advantages in saving quantum resources.
Parallel Computing of Graph-based Functions in ReRAM
Authors: Froehlich Saman , Shirinzadeh Saeideh , Drechsler Rolf
Published: January 2022

Resistive Random Access Memory (ReRAM) is an emerging non-volatile memory technology. Besides its low power consumption and its high scalability, its inherent computation capabilities make ReRAM especially interesting for future computer architectures. Merging computations into the memory is a promising solution for overcoming the memory bottleneck.

To perform computations in ReRAM, efficient synthesis strategies for Boolean functions have to be developed. In this article, we give a thorough presentation of how to employ parallel computing capabilities of ReRAM for the synthesis of functions given state-of-the-art graph-based representations AIGs or BDDs. Additionally, we introduce a new graph-based representation called m-And-Inverter Graph (m-AIGs), which allows us to fully exploit the computing capabilities of ReRAM. In the simulations, we show that our proposed approaches outperform state-of-the art synthesis strategies, and we show the superiority of m-AIGs over the standard AIG representation for ReRAM-based synthesis.
Accelerating On-Chip Training with Ferroelectric-Based Hybrid Precision Synapse
Authors: Luo Yandong , Wang Panni , Yu Shimeng
Published: January 2022

In this article, we propose a hardware accelerator design using
ferroelectric transistor (FeFET)-based hybrid precision synapse (HPS)
for
deep neural network (DNN)
on-chip training. The drain erase scheme for FeFET programming is incorporated for both FeFET HPS design and FeFET buffer design. By using drain erase, high-density FeFET buffers can be integrated onchip to store the intermediate input-output activations and gradients, which reduces the energy consuming off-chip DRAM access. Architectural evaluation results show that the energy efficiency could be improved by 1.2× ∼ 2.1×, 3.9× ∼ 6.0× compared to the other HPS-based designs and emerging non-volatile memory baselines, respectively. The chip area is reduced by 19% ∼ 36% compared with designs using SRAM on-chip buffer even though the capacity of FeFET buffer is increased. Besides, by utilizing drain erase scheme for FeFET programming, the chip area is reduced by 11% ∼ 28.5% compared with the designs using body erase scheme.
Bounded Abstract Effects
Authors: Melicher Darya , Xu Anlun , Zhao Valerie , Potanin Alex , Aldrich Jonathan
Published: January 2022

Effect systems have been a subject of active research for nearly four decades, with the most notable practical example being checked exceptions in programming languages such as Java. While many exception systems support abstraction, aggregation, and hierarchy (e.g., via class declaration and subclassing mechanisms), it is rare to see such expressive power in more generic effect systems. We designed an effect system around the idea of protecting system resources and incorporated our effect system into the Wyvern programming language. Similar to type members, a Wyvern object can have effect members that can abstract lower-level effects, allow for aggregation, and have both lower and upper bounds, providing for a granular effect hierarchy. We argue that Wyvern’s effects capture the right balance of expressiveness and power from the programming language design perspective. We present a full formalization of our effect-system design, showing that it allows reasoning about authority and attenuation. Our approach is evaluated through a security-related case study.
Dynamic Graph Reasoning for Conversational Open-Domain Question Answering
Authors: Li Yongqi , Li Wenjie , Nie Liqiang
Published: January 2022

In recent years, conversational agents have provided a natural and convenient access to useful information in people’s daily life, along with a broad and new research topic, conversational question answering (QA). On the shoulders of conversational QA, we study the conversational open-domain QA problem, where users’ information needs are presented in a conversation and exact answers are required to extract from the Web. Despite its significance and value, building an effective conversational open-domain QA system is non-trivial due to the following challenges: (1) precisely understand conversational questions based on the conversation context; (2) extract exact answers by capturing the answer dependency and transition flow in a conversation; and (3) deeply integrate question understanding and answer extraction. To address the aforementioned issues, we propose an end-to-end Dynamic Graph Reasoning approach to Conversational open-domain QA (DGRCoQA for short). DGRCoQA comprises three components, i.e., a dynamic question interpreter (DQI), a graph reasoning enhanced retriever (GRR), and a typical Reader, where the first one is developed to understand and formulate conversational questions while the other two are responsible to extract an exact answer from the Web. In particular, DQI understands conversational questions by utilizing the QA context, sourcing from predicted answers returned by the Reader, to dynamically attend to the most relevant information in the conversation context. Afterwards, GRR attempts to capture the answer flow and select the most possible passage that contains the answer by reasoning answer paths over a dynamically constructed
context graph
. Finally, the Reader, a reading comprehension model, predicts a text span from the selected passage as the answer. DGRCoQA demonstrates its strength in the extensive experiments conducted on a benchmark dataset. It significantly outperforms the existing methods and achieves the state-of-the-art performance.
SolType: refinement types for arithmetic overflow in solidity
Authors: Tan Bryan , Mariano Benjamin , Lahiri Shuvendu K. , Dillig Isil , Feng Yu
Published: January 2022

As smart contracts gain adoption in financial transactions, it becomes increasingly important to ensure that they are free of bugs and security vulnerabilities. Of particular relevance in this context are arithmetic overflow bugs, as integers are often used to represent financial assets like account balances. Motivated by this observation, this paper presents SolType, a refinement type system for Solidity that can be used to prevent arithmetic over- and under-flows in smart contracts. SolType allows developers to add refinement type annotations and uses them to prove that arithmetic operations do not lead to over- and under-flows. SolType incorporates a rich vocabulary of refinement terms that allow expressing relationships between integer values and aggregate properties of complex data structures. Furthermore, our implementation, called Solid, incorporates a type inference engine and can automatically infer useful type annotations, including non-trivial contract invariants.

To evaluate the usefulness of our type system, we use Solid to prove arithmetic safety of a total of 120 smart contracts. When used in its fully automated mode (i.e., using Solid's type inference capabilities), Solid is able to eliminate 86.3% of redundant runtime checks used to guard against overflows. We also compare Solid against a state-of-the-art arithmetic safety verifier called VeriSmart and show that Solid has a significantly lower false positive rate, while being significantly faster in terms of verification time.
Learning formulas in finite variable logics
Authors: Krogmeier Paul , Madhusudan P.
Published: January 2022

We consider grammar-restricted exact learning of formulas and terms in finite variable logics. We propose a novel and versatile automata-theoretic technique for solving such problems. We first show results for learning formulas that classify a set of positively- and negatively-labeled structures. We give algorithms for realizability and synthesis of such formulas along with upper and lower bounds. We also establish positive results using our technique for other logics and variants of the learning problem, including first-order logic with least fixed point definitions, higher-order logics, and synthesis of queries and terms with recursively-defined functions.
Context-bounded verification of thread pools
Authors: Baumann Pascal , Majumdar Rupak , Thinniyam Ramanathan S. , Zetzsche Georg
Published: January 2022

Thread pooling is a common programming idiom in which a fixed set of worker threads are maintained to execute tasks concurrently. The workers repeatedly pick tasks and execute them to completion. Each task is sequential, with possibly recursive code, and tasks communicate over shared memory. Executing a task can lead to more new tasks being spawned. We consider the safety verification problem for thread-pooled programs. We parameterize the problem with two parameters: the size of the thread pool as well as the number of context switches for each task. The size of the thread pool determines the number of workers running concurrently. The number of context switches determines how many times a worker can be swapped out while executing a single task---like many verification problems for multithreaded recursive programs, the context bounding is important for decidability.

We show that the safety verification problem for thread-pooled, context-bounded, Boolean programs is EXPSPACE-complete, even if the size of the thread pool and the context bound are given in binary. Our main result, the EXPSPACE upper bound, is derived using a sequence of new succinct encoding techniques of independent language-theoretic interest. In particular, we show a polynomial-time construction of downward closures of languages accepted by succinct pushdown automata as doubly succinct nondeterministic finite automata. While there are explicit doubly exponential lower bounds on the size of nondeterministic finite automata accepting the downward closure, our result shows these automata can be compressed. We show that thread pooling significantly reduces computational power: in contrast, if only the context bound is provided in binary, but there is no thread pooling, the safety verification problem becomes 3EXPSPACE-complete. Given the high complexity lower bounds of related problems involving binary parameters, the relatively low complexity of safety verification with thread-pooling comes as a surprise.
Extending Intel-x86 consistency and persistency: formalising the semantics of Intel-x86 memory types and non-temporal stores
Authors: Raad Azalea , Maranget Luc , Vafeiadis Viktor
Published: January 2022

Existing semantic formalisations of the Intel-x86 architecture cover only a small fragment of its available features that are relevant for the
consistency
semantics of multi-threaded programs as well as the
persistency
semantics of programs interfacing with non-volatile memory.

We extend these formalisations to cover: (1) non-temporal writes, which provide higher performance and are used to ensure that updates are flushed to memory; (2) reads and writes to other Intel-x86 memory types, namely uncacheable, write-combined, and write-through; as well as (3) the interaction between these features. We develop our formal model in both operational and declarative styles, and prove that the two characterisations are equivalent. We have empirically validated our formalisation of the consistency semantics of these additional features and their subtle interactions by extensive testing on different Intel-x86 implementations.
PRIMA: general and precise neural network certification via scalable convex hull approximations
Authors: Müller Mark Niklas , Makarchuk Gleb , Singh Gagandeep , Püschel Markus , Vechev Martin
Published: January 2022

Formal verification of neural networks is critical for their safe adoption in real-world applications. However, designing a precise and scalable verifier which can handle different activation functions, realistic network architectures and relevant specifications remains an open and difficult challenge.

In this paper, we take a major step forward in addressing this challenge and present a new verification framework, called PRIMA. PRIMA is both (i) general: it handles any non-linear activation function, and (ii) precise: it computes precise convex abstractions involving
multiple
neurons via novel convex hull approximation algorithms that leverage concepts from computational geometry. The algorithms have polynomial complexity, yield fewer constraints, and minimize precision loss.

We evaluate the effectiveness of PRIMA on a variety of challenging tasks from prior work. Our results show that PRIMA is significantly more precise than the state-of-the-art, verifying robustness to input perturbations for up to 20%, 30%, and 34% more images than existing work on ReLU-, Sigmoid-, and Tanh-based networks, respectively. Further, PRIMA enables, for the first time, the precise verification of a realistic neural network for autonomous driving within a few minutes.
Fully abstract models for effectful λ-calculi via category-theoretic logical relations
Authors: Kammar Ohad , Katsumata Shin-ya , Saville Philip
Published: January 2022

We present a construction which, under suitable assumptions, takes a model of Moggi’s computational λ-calculus with sum types, effect operations and primitives, and yields a model that is adequate and fully abstract. The construction, which uses the theory of fibrations, categorical glueing, ⊤⊤-lifting, and ⊤⊤-closure, takes inspiration from O’Hearn & Riecke’s fully abstract model for PCF. Our construction can be applied in the category of sets and functions, as well as the category of diffeological spaces and smooth maps and the category of quasi-Borel spaces, which have been studied as semantics for differentiable and probabilistic programming.
Solving string constraints with Regex-dependent functions through transducers with priorities and variables
Authors: Chen Taolue , Flores-Lamas Alejandro , Hague Matthew , Han Zhilei , Hu Denghang , Kan Shuanglong , Lin Anthony W. , Rümmer Philipp , Wu Zhilin
Published: January 2022

Regular expressions are a classical concept in formal language theory. Regular expressions in programming languages (RegEx) such as JavaScript, feature non-standard semantics of operators (e.g. greedy/lazy Kleene star), as well as additional features such as capturing groups and references. While symbolic execution of programs containing RegExes appeals to string solvers natively supporting important features of RegEx, such a string solver is hitherto missing. In this paper, we propose the first string theory and string solver that natively provides such support. The key idea of our string solver is to introduce a new automata model, called prioritized streaming string transducers (PSST), to formalize the semantics of RegEx-dependent string functions. PSSTs combine priorities, which have previously been introduced in prioritized finite-state automata to capture greedy/lazy semantics, with string variables as in streaming string transducers to model capturing groups. We validate the consistency of the formal semantics with the actual JavaScript semantics by extensive experiments. Furthermore, to solve the string constraints, we show that PSSTs enjoy nice closure and algorithmic properties, in particular, the regularity-preserving property (i.e., pre-images of regular constraints under PSSTs are regular), and introduce a sound sequent calculus that exploits these properties and performs propagation of regular constraints by means of taking post-images or pre-images. Although the satisfiability of the string constraint language is generally undecidable, we show that our approach is complete for the so-called straight-line fragment. We evaluate the performance of our string solver on over 195000 string constraints generated from an open-source RegEx library. The experimental results show the efficacy of our approach, drastically improving the existing methods (via symbolic execution) in both precision and efficiency.