Type Checking Research Articles

Ligation-free single scrotal incision orchiectomy with ultrasonic scalpel: Xinhua Zhang Procedure

Background: To explore the efficacy and safety of a new type of testicular excision with ultrasonic dissector. Methods: A retrospective analysis was performed on 69 patients with advanced prostate cancer undergoing orchiectomy in our hospital between June 2017 and June 2019. All patients were divided into a traditional surgery group (n = 27) and an ultrasonic scalpel surgery group (n = 42). The operation time, intraoperative blood loss, postoperative hospital stay and postoperative complication rates were compared. Results: The ultrasonic scalpel surgery group had significantly shorter operation times and less intraoperative blood loss than the traditional surgery group (each P < 0.01). Moreover, the incidence of postoperative complication differed significantly between the traditional surgery group (18.52%) and the ultrasonic scalpel surgery group (0%) (P < 0.01). However, there was no significant difference in postoperative hospital stay between the two groups (P > 0.05). Conclusions: The surgery time for testicular excision using the ultrasonic knife is short, the operation is simple and the complications are few and thus it may become a form of replacement for traditional testicular excision.

Cubical Agda: A dependently typed programming language with univalence and higher inductive types

AbstractProof assistants based on dependent type theory provide expressive languages for both programming and proving within the same system. However, all of the major implementations lack powerful extensionality principles for reasoning about equality, such as function and propositional extensionality. These principles are typically added axiomatically which disrupts the constructive properties of these systems. Cubical type theory provides a solution by giving computational meaning to Homotopy Type Theory and Univalent Foundations, in particular to the univalence axiom and higher inductive types (HITs). This paper describes an extension of the dependently typed functional programming language Agda with cubical primitives, making it into a full-blown proof assistant with native support for univalence and a general schema of HITs. These new primitives allow the direct definition of function and propositional extensionality as well as quotient types, all with computational content. Additionally, thanks also to copatterns, bisimilarity is equivalent to equality for coinductive types. The adoption of cubical type theory extends Agda with support for a wide range of extensionality principles, without sacrificing type checking and constructivity.

Relational cost analysis in a functional-imperative setting

Abstract Relational cost analysis aims at formally establishing bounds on the difference in the evaluation costs of two programs. As a particular case, one can also use relational cost analysis to establish bounds on the difference in the evaluation cost of the same program on two different inputs. One way to perform relational cost analysis is to use a relational type-and-effect system that supports reasoning about relations between two executions of two programs. Building on this basic idea, we present a type-and-effect system, called ARel, for reasoning about the relative cost (the difference in the evaluation cost) of array-manipulating, higher order functional-imperative programs. The key ingredient of our approach is a new lightweight type refinement discipline that we use to track relations (differences) between two mutable arrays. This discipline combined with Hoare-style triples built into the types allows us to express and establish precise relative costs of several interesting programs that imperatively update their data. We have implemented ARel using ideas from bidirectional type checking.

Localized Lama Gradual Typing

Gradual typing is a modern approach for combining benefits of static typing and dynamic typing. Although scientific research aim for soundness of type systems, many of languages intentionally make their type system unsound for speeding up performance. This paper describes an implementation of a dialect for Lama programming language that supports gradual typing with explicit annotation of dangerous parts of code. The target of current implementation is to grant type safety to programs while keeping their power of untyped expressiveness. This paper covers implementation issues and properties of created type system. Finally, some perspectives on improving precision and soundness of type system are discussed.

Long-term durability and environmental safety of slurry type of coal ash mixed material

The combustion processes in coal-fired power plants generate a huge amount of coal fly ash (FA) as by-products. In Japan, there has been a continuous annual increase in the emission of FA due to the increased operation of thermal power stations after the Great East Japan Earthquake, which occurred in 2011. However, effectively harnessing these produced ashes has been a challenge. Coal ash mixed materials (CAMMs) (FA, cement and water composite) are being exploited mainly for the construction of port infrastructures in Japan, but their usage has been so far limited. One of the reasons for the lack of effective utilisation is that there are limited research opportunities and knowledge on the long-term durability of CAMM. Hence, this study evaluated the durability of CAMM under different exposure environments (atmospheric curing, water immersion and seawater immersion) in order to provide more understanding of the long-term application of CAMM. Results from this study indicated that the strength of CAMM increases with an increase in cement addition and curing days. However, under seawater exposure conditions, it is probable that the strength decreases after 1 year due to leaching of calcium ions from the CAMM. The deterioration of CAMM starts from the surface. Therefore, in conditions where direct contact with seawater is conceivable, attention should be paid to long-term durability.

Lolisa: Formal Syntax and Semantics for a Subset of the Solidity Programming Language in Mathematical Tool Coq

The security of blockchain smart contracts is one of the most emerging issues of the greatest interest for researchers. This article presents an intermediate specification language for the formal verification of Ethereum-based smart contract in Coq, denoted as Lolisa. The formal syntax and semantics of Lolisa contain a large subset of the Solidity programming language developed for the Ethereum blockchain platform. To enhance type safety, the formal syntax of Lolisa adopts a stronger static type system than Solidity. In addition, Lolisa includes a large subset of Solidity syntax components as well as general-purpose programming language features. Therefore, Solidity programs can be directly translated into Lolisa with line-by-line correspondence. Lolisa is inherently generalizable and can be extended to express other programming languages. Finally, the syntax and semantics of Lolisa have been encapsulated as an interpreter in mathematical tool Coq. Hence, smart contracts written in Lolisa can be symbolically executed and verified in Coq.

Botulinum toxin type A therapy for hemifacial spasm.

This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles innervated by the facial nerve. It is a chronic disorder, and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and intramuscular injections with botulinum toxin type A (BtA). To compare the efficacy, safety, and tolerability of BtA versus placebo in people with HFS. We searched CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. We ran the electronic database search, with no language restrictions, in July 2020. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with HFS. Two review authors independently assessed records. We planned to select included studies, extract data using a paper pro forma, and evaluate the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We planned to perform meta-analyses. The primary efficacy outcome was HFS-specific improvement. The primary safety outcome was the proportion of participants with any adverse event. We found no parallel-group randomised controlled trials comparing BtA and placebo in HFS. We did not find any randomised trials that evaluated the efficacy and safety of botulinum toxin type A in people with hemifacial spasm, so we are unable to draw any conclusions. Observational data show a strong association between BtA treatment and symptom improvement, and a favourable safety profile. While it is unlikely that future placebo-controlled RCTs will evaluate absolute efficacy and safety, they should address relevant questions for both people with HFS (such as long-term effects, quality of life, and other patient-reported outcomes), and clinicians (such as relative effectiveness of different BtA formulations and schemes of treatment) to better guide clinical practice.).

Knowing when to ask: sound scheduling of name resolution in type checkers derived from declarative specifications

There is a large gap between the specification of type systems and the implementation of their type checkers, which impedes reasoning about the soundness of the type checker with respect to the specification. A vision to close this gap is to automatically obtain type checkers from declarative programming language specifications. This moves the burden of proving correctness from a case-by-case basis for concrete languages to a single correctness proof for the specification language. This vision is obstructed by an aspect common to all programming languages: name resolution. Naming and scoping are pervasive and complex aspects of the static semantics of programming languages. Implementations of type checkers for languages with name binding features such as modules, imports, classes, and inheritance interleave collection of binding information (i.e., declarations, scoping structure, and imports) and querying that information. This requires scheduling those two aspects in such a way that query answers are stable—i.e., they are computed only after all relevant binding structure has been collected. Type checkers for concrete languages accomplish stability using language-specific knowledge about the type system. In this paper we give a language-independent characterization of necessary and sufficient conditions to guarantee stability of name and type queries during type checking in terms of critical edges in an incomplete scope graph . We use critical edges to give a formal small-step operational semantics to a declarative specification language for type systems, that achieves soundness by delaying queries that may depend on missing information. This yields type checkers for the specified languages that are sound by construction—i.e., they schedule queries so that the answers are stable, and only accept programs that are name- and type-correct according to the declarative language specification. We implement this approach, and evaluate it against specifications of a small module and record language, as well as subsets of Java and Scala.

Automatic and efficient variability-aware lifting of functional programs

A software analysis is a computer program that takes some representation of a software product as input and produces some useful information about that product as output. A software product line encompasses many software product variants, and thus existing analyses can be applied to each of the product variations individually, but not to the entire product line as a whole. Enumerating all product variants and analyzing them one by one is usually intractable due to the combinatorial explosion of the number of product variants with respect to product line features. Several software analyses (e.g., type checkers, model checkers, data flow analyses) have been redesigned/re-implemented to support variability. This usually requires a lot of time and effort, and the variability-aware version of the analysis might have new errors/bugs that do not exist in the original one. Given an analysis program written in a functional language based on PCF, in this paper we present two approaches to transforming (lifting) it into a semantically equivalent variability-aware analysis. A light-weight approach (referred to as shallow lifting ) wraps the analysis program into a variability-aware version, exploring all combinations of its input arguments. Deep lifting, on the other hand, is a program rewriting mechanism where the syntactic constructs of the input program are rewritten into their variability-aware counterparts. Compositionally this results in an efficient program semantically equivalent to the input program, modulo variability. We present the correctness criteria for functional program lifting, together with correctness proof sketches of shallow lifting. We evaluate our approach on a set of program analyses applied to the BusyBox C-language product line.

A systematic approach to deriving incremental type checkers

Static typing can guide programmers if feedback is immediate. Therefore, all major IDEs incrementalize type checking in some way. However, prior approaches to incremental type checking are often specialized and hard to transfer to new type systems. In this paper, we propose a systematic approach for deriving incremental type checkers from textbook-style type system specifications. Our approach is based on compiling inference rules to Datalog, a carefully limited logic programming language for which incremental solvers exist. The key contribution of this paper is to discover an encoding of the infinite typing relation as a finite Datalog relation in a way that yields efficient incremental updates. We implemented the compiler as part of a type system DSL and show that it supports simple types, some local type inference, operator overloading, universal types, and iso-recursive types.

Formulog: Datalog for SMT-based static analysis

Satisfiability modulo theories (SMT) solving has become a critical part of many static analyses, including symbolic execution, refinement type checking, and model checking. We propose Formulog, a domain-specific language that makes it possible to write a range of SMT-based static analyses in a way that is both close to their formal specifications and amenable to high-level optimizations and efficient evaluation. Formulog extends the logic programming language Datalog with a first-order functional language and mechanisms for representing and reasoning about SMT formulas; a novel type system supports the construction of expressive formulas, while ensuring that neither normal evaluation nor SMT solving goes wrong. Our case studies demonstrate that a range of SMT-based analyses can naturally and concisely be encoded in Formulog, and that — thanks to this encoding — high-level Datalog-style optimizations can be automatically and advantageously applied to these analyses.

Multiparty motion coordination: from choreographies to robotics programs

We present a programming model and typing discipline for complex multi-robot coordination programming. Our model encompasses both synchronisation through message passing and continuous-time dynamic motion primitives in physical space. We specify continuous-time motion primitives in an assume-guarantee logic that ensures compatibility of motion primitives as well as collision freedom. We specify global behaviour of programs in a choreographic type system that extends multiparty session types with jointly executed motion primitives, predicated refinements, as well as a separating conjunction that allows reasoning about subsets of interacting robots. We describe a notion of well-formedness for global types that ensures motion and communication can be correctly synchronised and provide algorithms for checking well-formedness, projecting a type, and local type checking. A well-typed program is communication safe , motion compatible , and collision free . Our type system provides a compositional approach to ensuring these properties. We have implemented our model on top of the ROS framework. This allows us to program multi-robot coordination scenarios on top of commercial and custom robotics hardware platforms. We show through case studies that we can model and statically verify quite complex manoeuvres involving multiple manipulators and mobile robots---such examples are beyond the scope of previous approaches.

The Anatomy of the Temporal and Zygomatic Branches of the Facial Nerve: Application to Crow's Feet Wrinkles.

Advances in the understanding of wrinkling crow's feet while improving the safety and efficacy of botulinum toxin type A injection has pointed to drug dispersion in the lateral orbital wrinkles as a cause of adverse events of botulinum toxin type A injection. The purpose of this study is to identify the distribution of temporal and zygomatic branches of facial nerve in the orbicularis oculi muscles. Anatomical dissection of cadavers was performed in 31 cadavers, 13 females and 18 males, with ages ranging from 20 to 60 years, which of all had been embalmed by 10% formalin solution. The facial nerve was identified within subcutaneous tissue close periorbital region and both traced proximal and distal. Its temporal branch, zygomatic branch, facial and muscular entrance were located and accurately measured relative to established surface landmarks. Dissection of the facial nerve revealed 2 to 6 entrances of the temporal branch into the orbicularis oculi and 1 to 5 entrances of the zygomatic branch into the orbicularis oculi. Concerning the measurements of neural entering points, distance and angle from orbicularis oculi muscle to lateral ocular angle, a distribution map of its muscular entrance and their patterns of distribution were constructed. According to the dense area of the coordinate map, there were 3 points determined as the muscular entrance points to established surface landmarks. An anatomical dissection of cadavers was performed to identify the distribution of temporal and zygomatic branches of the facial nerve in the orbicularis oculi. According to the dense area of the coordinate map, the surface landmarks of 3 points were established as the muscular entrance of the facial nerve (MEF).

Multi‐view city‐based approach for code‐smell evolution visualisation

Code smells are indicators of inappropriate and possibly harmful design decisions that could lead to issues in the comprehensibility and maintainability of software systems. To avoid such quality complications, understanding the presence and prioritising the removal of code smells are required. This study presents a visualisation approach to help better understanding the evolutional characteristics of code smells presented in the different versions of the software system. The core of the visualisation approach is the metaphor of buildings and building blocks. An overall framework for detecting, categorising and visualising code smells is proposed. Three types of code smells were considered in this study. The considered code smells are God Class, Long Method and Type Checking. The applicability of the proposed approach is demonstrated by evaluating several versions of an open-source java software and visualising the detected code smells. Additionally, a pilot experimental study is conducted to empirically assure the usefulness of the proposed visualisations.

Apatinib combined with chemotherapy or concurrent chemo-brachytherapy in patients with recurrent or advanced cervical cancer: A phase II, randomized controlled, prospective study

Objectives: Apatinib mesylate is a novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which has exhibited good drug safety and clinical efficacy in several types of solid tumors. The present study aimed to assess the clinical efficacy and safety of apatinib combined with chemotherapy and concurrent chemobrachytherapy (CCBT) in patients with recurrent and advanced cervical cancer.

Efficacy and safety of IncobotulinumtoxinA in the treatment of lower limb spasticity in Japanese subjects

Objective: To confirm the efficacy and safety of botulinum toxin type A (BoNT-A) treatment incobotulinumtoxinA (INCO; Xeomin®, Merz Pharmaceuticals GmbH) in Japanese subjects from study sites in Japan with post-stroke spasticity in the lower limb (LL), using the Modified Ashworth Scale (MAS) spasticity score for the plantar flexors.

Obsidian

Blockchain platforms are coming into use for processing critical transactions among participants who have not established mutual trust. Many blockchains are programmable, supporting smart contracts , which maintain persistent state and support transactions that transform the state. Unfortunately, bugs in many smart contracts have been exploited by hackers. Obsidian is a novel programming language with a type system that enables static detection of bugs that are common in smart contracts today. Obsidian is based on a core calculus, Silica, for which we proved type soundness. Obsidian uses typestate to detect improper state manipulation and uses linear types to detect abuse of assets. We integrated a permissions system that encodes a notion of ownership to allow for safe, flexible aliasing. We describe two case studies that evaluate Obsidian’s applicability to the domains of parametric insurance and supply chain management, finding that Obsidian’s type system facilitates reasoning about high-level states and ownership of resources. We compared our Obsidian implementation to a Solidity implementation, observing that the Solidity implementation requires much boilerplate checking and tracking of state, whereas Obsidian does this work statically.

TrustFlow-X

This article addresses the challenges of memory safety in life-critical medical devices. Since the last decade, healthcare manufacturers have embraced the Internet of Things, pushing technological innovations to increase market share. Medical devices, including the most critical ones, tend to be increasingly connected to the Internet. Unfortunately, as critical devices often rely on unsafe programming languages such as C, they are no exception to memory safety issues. Given a memory vulnerability, a skillful attacker can take over a system and perform remote code execution. Combined with the fact that medical devices directly impact the safety of their users, a security vulnerability can lead to disastrous scenarios. To address this issue, this article presents TrustFlow-X, a novel hardware/software co-designed framework that provides efficient fine-grained control-flow integrity protection against memory-based attacks. The TrustFlow-X framework is composed of an LLVM-based compiler toolchain that generates a secure code. This secure code is then executed on an extended RISC-V processor that keeps track of sensitive data using a trusted memory. The obtained results show that the contribution is practical, providing a high level of trust in life-critical embedded systems.

Long-term efficacy and safety of a new botulinum toxin type A preparation in mouse gastrocnemius muscle

A new type A botulinum toxin (BoNT/A) preparation, JTM201 (NCBI chromosomal DNA ID: CP046450), has been developed, which comprises 900-kDa complexed toxin purified from Clostridium botulinum (strain: NCTC13319), but its safety and efficacy have not yet been evaluated. The purpose of this study was to evaluate the long-term efficacy and safety of JTM201 at different concentrations in comparison to another commercially available BoNT/A product, Botox® (onabotulinumtoxin A, ONA), using a mouse model. The LD50 of JTM201 was similar to that of ONA, but the intrinsic activity of JTM201 was higher than that of ONA. Functional recovery of the nerves and muscles in SKH-1 mice after administration of the two BoNT/A preparations (JTM201 and ONA) to the right gastrocnemius muscle was observed over 24 weeks. In addition, JTM201 did not induce any skin or muscle inflammatory response in 24 weeks. Paralysis induced by neurotransmitter blockade after JTM201 administration was comparable to that of ONA treatment. Both muscle weight and volume decreased in a concentration-dependent manner following JTM201 or ONA toxin injection until week 4. Reduced muscle fiber size due to atrophy and consequent fibrosis were detected following injection of JTM201 or ONA. Moreover, we assessed the extent of diffusion of JTM201 or ONA to the tibialis anterior and quadriceps femoris muscles, demonstrating limited diffusion to off-target muscles. In conclusion, JTM201 demonstrated long-term efficacy and safety equivalent to those of ONA based on compound muscle action potential, muscle volume, and histology analyses. These data suggest that JTM201 is a new BoNT/A formulation with safety and efficacy comparable to those of ONA.

1313P Phase III LEAP-006 safety run-in (Part 1): 1L pembrolizumab (Pembro) + chemotherapy (Chemo) with lenvatinib (Len) for metastatic NSCLC

Pembro + platinum-based chemo is standard 1L therapy for patients (pts) with metastatic NSCLC. In a phase 1b/2 study, pembro + len showed antitumor activity with acceptable safety in multiple tumor types, including metastatic NSCLC treated with ≤2 prior regimens. LEAP-006 (NCT03829319) evaluates 1L pembro + platinum-based chemo ± len in pts with metastatic nonsquamous (nsq) NSCLC. We report the first data from the open-label safety run-in (part 1) of LEAP-006. LEAP-006 is a global, randomized, double-blind, placebo (pbo)-controlled, 2-part, phase 3 study enrolling pts aged ≥18 y with metastatic, treatment-naive nsqNSCLC, ECOG PS 0/1, and tumor sample available for PD-L1 expression; and without actionable genetic aberrations. In part 1, pts received len 8 mg/d + pembro 200 mg + pemetrexed (pem) 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W in cycles 1‒4; then pembro (up to 31 more cycles) with len + pem until PD/toxicity. Dose-limiting toxicities (DLTs; selected prespecified grade ≥3 AEs or prespecified criteria for thrombocytopenia or any grade thromboembolic event) were assessed for 21 d after first dose. 13 pts were enrolled and treated in part 1 (data cutoff, Mar 3, 2020; median study follow-up, 7.5 [range, 5.7–10.3] mo). Pts received a median of 10 (range, 2–12) cycles of therapy. There were 2 DLTs–both grade 3 hyponatremia in pts receiving cisplatin. 10 pts (77%) had grade 3–5 AEs (treatment-related, n = 7 [54%]), 1 (8%) died due to an AE (not treatment-related), and 6 (46%) had immune-mediated AEs. 4 pts (31%) had grade 3 hypertension; none had grade ≥3 proteinuria. There were no infusion reactions. ORR was 69.2% (95% CI, 38.6-90.9; n = 9; all PR); 3 pts (23.1%) had SD. Of 13 pts, 11 were alive and 10 were progression free by BICR. As <3 DLTs occurred in each platinum-containing arm, enrollment into part 2 began, in which pts randomly receive platinum-based chemo + pembro (similar to part 1) with either len or pbo. Results from part 1 showed acceptable safety and tolerability, and preliminary evidence of antitumor activity with 1L len + pembro + platinum-based chemo in pts with metastatic nsqNSCLC. Enrollment in part 2 is ongoing.